https://pubmed.ncbi.nlm.nih.gov/17166350/
===================================================Objective:
To explore whether propofol plays a protective role in kidney injury during acute respiratory distress syndrome (ARDS) by affecting the expression of Gq/11 protein.
Methods:
An ARDS model in rats was reproduced by intravenous injection of oleic acid (OA). Healthy Wistar rats were randomly divided into pre-treatment group in which rats received propofol before given OA (P group), OA group with rats received propofol 90 minutes after iv OA (OA group), and control group (C group). Blood pressure, plasma and kidney homogenate contents of angiotensin-conversion enzyme (ACE), lactate dehydrogenase (LDH) activity, and malondialdehyde (MDA) were assessed during the experimental period, and the concentration of Gq/11 protein was determined by Western blot.
Results:
The concentration of Gq/11 protein of P group [(124.68±19.38)%] was increased (24.68±19.38)% compared with C group [(100.00±0)%, P < 0.013, and it was obviously decreased compared with OA group [(149.34±20.04)%, P < 0.013. ACE ((16.52 ± 1.37) μmol·min^-1·g^-1), LDH activity ((1.20 ± 0.16) kU/g], and MDA content [(1.51±0.35) μmol/g], respectively, in homogenate of P group were lower than OA group [(17.56±1.02) μmol·min^-1·g^-1, (1.41±0.16) kU/g, (1.94 ±0.16) μmol/g, respectively, all P < 0.013.
Conclusion:
Pre-treatment with propofol can reduce the concentration of Gq/11 protein in kidney tissue, and it can ameliorate the injury to the kidney during ARDS.
Ma Qi, Kelala A, Zhang Jianlong, Zhang Li, Li Shiyong, Wang Junfang - "The protective effect of propofol on cardiac function damage during ARDS and its correlation with Gq/11 protein" Journal of Xinjiang Medical University 4:312-314 (2005) PFPC Library
===================================================Objective:
To observe the alterations of heart function and expression of cardiac Gq/11 protein during acute respiratory distress syndrome, and the changes after injecting propofol. Investigated the mechanism of cardiac insufficiency and the change of expression of cardiac Gq/11 protein and the protective effects of propofol, to provide theoretical basis for ARDS on the molecular level.
Methods:
The rat model was made by injection OA from caudal vena. Twenty-four male Wistar rats were randomly divided into three groups: control group (C group), propofol group (P group), and experiment group (OA group). Heart function indexes were measured from the right carotid. The levels of LDH, CK, MDA in plasma and cardiac tissue were measured. The expression of cardiac Gq/11 protein was measured.
Results:
LVSP decreased in P group and OA group, compared with C group, P < 0.01; +dp/dtmax decreased in OA group, compared with C group, P < 0.01. -dp/dtmax showed the same change as LVSP. The plasma levels of LDH increased in OA group, compared with C group and P group P < 0.01; the levels of LDH in cardiac tissue were lowest in C group, and highest in OA group (P < 0.01). The changes of the levels of CK, MDA in plasma and cardiac tissue were the same as the change of LDH in cardiac tissue; expression of Gq/11 protein was increased in OA group and P group (P < 0.01).
Conclusion:
Expression of Gq/11 protein upgraded during ARDS, it is important in cardiac injury, and the injury could be mitigated by the injection of propofol. The anti-oxidation of propofol may play a certain role in it.
Clara Abbas, Zhang Jianlong, Zhang Li, Ma Qi, Wang Junfang, Li Shiyong - "The dynamic alteration of Gq/11 protein concentration in the heart of rats during acute respiratory distress syndrome (ARDS)" Journal of Xinjiang Medical University 4:308-311 (2005) PFPC Library
===================================================Objective:
To observe the dynamic changes of Gq/11 protein in the heart of rats during acute respiratory distress syndrome (ARDS) and to further elucidate the pathogenesis of ARDS complicated by multiple organ dysfunction at the molecular level.
Methods:
40 male Wistar rats were selected, the rat ARDS model was replicated by tail vein injection of oleic acid (oleic acid, OA 0.2ml/kg), and they were divided into a control group (C group) and an oleic acid group (OA group). They were further divided into four subgroups of 30, 60, 90, and 120 min according to different time limits. Blood gases, mean arterial blood pressure (MAP), cardiac function (LVSP, left ventricular ± dp/dtmax), plasma and myocardial MDA content, and LDH and CK activity were detected. The Western blotting method was used to detect cardiac Gq/11 protein content.
Results:
PaO2 and MAP in the OA group decreased progressively with time (P < 0.05～0.01). LVSP and left ventricular ± dp/dtmax gradually decreased, and the OA90 and 120 min groups were significantly lower than those in the C group (P < 0.01). In the OA group, except for 30 minutes, the plasma MDA content and LDH activity were significantly higher than those in the C group (P < 0.01), and the plasma CK activity began to increase 30 minutes after the injection of OA (P < 0.01). Myocardial MDA content and LDH activity in each OA group were higher than those in group C and showed an increasing trend with time (P < 0.05~0.01). Myocardial CK activity was higher than that in group C except for the OA30min group (P < 0.01). Except for 30 minutes, the Gq/11 protein content in the OA group was (24.72±24.05)%, (40.61±22.41)%, and (50.84±24.49)% higher than that in the C group, respectively, over time.
Morphological observation:
The myocardial interstitial edema was mild in the OA30min group, a small amount of inflammatory cell infiltration and some myocardial cell lysis and necrosis were seen in the OA60min group, and more inflammatory cell infiltration was seen in the OA90 and 120min groups.
Conclusions:
Up-regulation of the expression of Gq/11 may play a role in heart injury during ARDS.
Zhang Li, Refat Bekchantaif, Wang Na, Clara Abbas - "Change of Gq protein-phosphatidyl inositol signaling in brain of rats with acute respiratory distress syndrome" Chinese Journal of Pathophysiology Issue 6:1134-1137 (2010) PFPC Library
===================================================Objective:
To explore the changes and role of the Gq protein-inositol phospholipid pathway in the brain tissue of rats with acute respiratory distress syndrome (ARDS).
Methods:
40 healthy male Wistar rats were randomly divided into oleic acid group (OA group) and control group. In the OA group, the ARDS model was replicated by injecting OA 0.2 mL/kg (within 2 minutes) into the tail vein of rats, and was divided into 4 subgroups of 30 min, 60 min, 90 min, and 120 min according to different observation time points. The mean arterial blood pressure (MABP), blood gas, malondialdehyde content in plasma and brain tissue, and lactate dehydrogenase (LDH) and creatine kinase (CK) activities of rats in each group were detected. Western blotting method was used to detect the content of Gq/11 protein α active subunit and phospholipase C (PLC) in the brain tissue of rats in each group.
Results:
Compared with the control group, MABP and PaO2 were significantly lower in the OA group (P < 0.05). The MDA content and LDH activity in plasma and brain tissue in the OA90 min and 120 min groups were significantly increased (P < 0.05). Plasma CK activity in the OA group was significantly higher than that in the control group (P < 0.05). Brain tissue CK activity increased in the OA 60 min group (P < 0.05), and then decreased in the 90 min and 120 min groups (P < 0.05). Brain tissue Gαq/11 protein was significantly increased in the OA60 min, 90 min, and 120 min groups (P < 0.05). The expression of PLC in the brain tissue of the OA group was significantly increased (P < 0.05). The expression of Gαq/11 protein in brain tissue was negatively correlated with changes in PaO2 (r = -0.579, P < 0.05), positively correlated with changes in MDA in brain tissue (r = 0.538, P < 0.05), and also positively correlated with changes in LDH in brain tissue (r = 0.624, P < 0.05).
Conclusion:
The enhanced activity of Gq protein-inositol phospholipid signaling pathway in ARDS may be involved in brain tissue damage.
Zhang L, Leifate B, Kelala A - "The dynamic alteration in Gq/11 protein expression in multiple organs during acute respiratory distress syndrome in rat" Chinese Critical Care Medicine 22(8):477-481 (2010) PMID: 20804650 PFPC Library
https://pubmed.ncbi.nlm.nih.gov/20804650/
===================================================Objective:
To explore the expression and role of Gq/11 protein in the lungs, brain, heart, kidney, liver, and small intestine of rats with acute respiratory distress syndrome (ARDS).
Methods:
40 Wistar rats were divided into 5 groups according to the random number table method. The ARDS model was replicated by injecting 0.2 ml/kg of oleic acid (OA) into the tail vein of rats. The control group was injected with an equal amount of normal saline from the tail vein. The plasma of the model group was measured at 30, 60, 90, and 120 minutes after modeling, and lactate dehydrogenase (LDH), malondialdehyde (MDA), and angiotensin-converting enzyme (ACE) in each organ. Western blotting was used to detect Gq/11 protein α active subunit Gαq/ in each organ.
Results:
Compared with the control group, LDH activity in the plasma and the heart 30 minutes after injection of OA gradually increased ( plasma (kU/L): 9.69±1.66 vs. 6.27±1.70, heart (kU/g): 0.81±0.12 vs. 0.59±0.09), and in the lung, brain, kidney, and small intestine 60 minutes after injection of OA also gradually increased (lung (kU/g): 1.15±0.19 vs. 0.87±0.11, brain (kU/g): 2.27±0.37 vs. 1.53±0.61, kidney (kU/g): 1.13±0.26 vs. 0.64 ±0.09, small intestine (kU/g): 0.72±0.10 vs. 0.60±0.13), and in the liver (kU/g) 90 minutes after injection of OA gradually increased (0.50±0.14 vs. 0.39±0.05, P〈 0.05 or P<0.01). MDA concentration in the heart (μmol/g) 30 minutes after injection of OA gradually increased (2.20±0.47 vs. 1.45±0.27), and after 60 minutes in the heart Plasma, lung, and kidney showed a progressive increase [plasma (μmol/L): 3.10±0.58 vs. 2.33±0.35, lung (μmol/g): 5.56±1.30 vs. 2.05±0.52, kidney (μmol/g): 1.61±0.27 vs. 0.98±0.42 ), and in the brain, liver, and small intestine 90 minutes after injection of OA gradually increased [brain (μmol/g): 6.78±1.38 vs. 5.83±1.58, liver (μmol/g): 2.58±0.68 vs. 2.11± 0.42, small intestine (μmol/g): 2.14±0.51 vs. 0.81±0.26, P<0.05 or P<0.01). ACE activity was reduced in the plasma and lung 60 minutes after injection of OA [plasma (μmol·min-1·L^-1): 15.47±1.68 vs. 19.87±3.11, lung (μmol·min^-1·g^-1): 20.61±1.81 vs. 26.26±1.93], but in the kidney (μmol· min^-1·g^-1) it was gradually increased (15.92±1.20 vs. 13.67±2.26), and in the small intestine (μmol·min^-1·g^-1) 90 minutes after injection of OA it gradually increased (4.42±0.34 vs. 3.29±0.24, all P<0.01). Gαq/11 protein expression in the lung and small intestine obviously increased 30 minutes after injection of OA [lung: (119.24±2.38)% vs. (100.00 ±18.74)%, small intestine: (138.91±23.03)% vs. (100.00±19.43)%], and in the brain, heart, and kidney increased 60 minutes after injection of OA [brain: (141.85±33.82)% vs. (100.00±16.81)%, heart: (124.72±24.05)% vs. (100.00±16.04)% , kidney: (123.98±25.74)% vs. (100.00±8.50)%], and showed a progressive increase in the liver after 90 minutes [(134.34±19.14)% vs. (100.00±13.04)%, P<0.05 or P<0.01]. A positive correlation between the change in Gαq/11 protein expression and LDH in these organs (r=0.584, P<0.05) was found.
Conclusion:
Up-regulation of Gq/11 protein expression in the lung, brain, heart, kidney, liver, and small intestine may induce abnormal activity of phosphatidyl inositol signal transduction and thus plays a role in the production of multiple organ injury during ARDS.
Clara Abbas, Liu Chunxi, Zhang Li, Liu Hongying, Chen Rong, Wang Weifeng, Li Xiujuan - "Dynamic changes of Gq/11 protein in the small intestine of experimental ARDS rats" Chinese Journal of Pathophysiology 8:1651-1652 (2005) PFPC Library
================================================Objective:
To observe the changes in Gq/11 protein in intestinal injury in rats with acute respiratory distress syndrome (ARDS).
Methods:
The rat ARDS model was created by injecting oleic acid into the tail vein. The oleic acid component was divided into four groups: 30 min, 60 min, 90 min, and 120 min according to the observation time limit. The Gq/11 protein content in the small intestinal mucosa was detected by Western blotting. Determination of ACE, LDH activity, and MDA content in plasma and small intestinal tissue homogenate.
Results:
In the small intestinal mucosa of the oleic acid group, the Gq/11 protein increased compared to the control group (P<0.05 or 0.01), and it showed an increasing trend with the extension of the observation time. The oleic acid group exhibited a decrease in plasma ACE activity (P<0.01), an increase in plasma LDH activity, and MDA content (P<0.01). In the small intestinal tissue, ACE, LDH activity, and MDA content gradually increased (P<0.05 or 0.01).
Conclusion:
(1) Oleic acid induces intestinal damage during the ARDS process. (2) The upregulation of intestinal Gq/11 protein suggests its possible involvement in the process of ARDS-induced intestinal injury, mediating the transmission of extracellular signals to the intracellular environment, leading to changes in intestinal function and structure.
Discussion:
Currently, it is believed that the key to the onset of ARDS is the activation of pathogenic factors that trigger cellular and humoral factors, resulting in excessive or uncontrolled inflammatory responses in the body. It is essentially a systemic inflammatory response syndrome (SIRS) manifested in the lungs during ARDS, and SIRS persists throughout ARDS. The "central organ of the disease in the intestine" theory proposes that the intestine may be the initiating organ during SIRS and also the target organ of SIRS.
The results of this study show that LDH activity and MDA content in plasma and small intestinal tissue gradually increased over time, indicating that the small intestine in the ARDS process has been subjected to lipid peroxidation damage, and intestinal barrier function has been impaired. The mechanism of changes in plasma and small intestinal tissue ACE activity may include: (1) The main site of ACE synthesis and release in plasma is damaged in the process of ARDS. (2) Low perfusion during SIRS activates the local renin-angiotensin system in the intestines, leading to arterial constriction, exacerbating intestinal ischemia and hypoxia.
Gq/11 protein, as a type of G protein, can couple with various hormones, peptides, and inflammatory mediators' receptors. The activation of these receptors activates Gq/11 protein, increases phospholipase C activity, generates inositol triphosphate and diacylglycerol, and produces a wide range of biological effects. This experiment aimed to explore whether the mediated inositol phospholipid signal transduction system participates in the mechanism of intestinal injury in ARDS rats by observing the changes in Gq/11 protein content in the small intestinal mucosa.
The results showed that the Gq/11 protein in the small intestinal mucosa of the oleic acid group significantly increased compared to the control group. With the extension of the observation time, the Gq/11 protein content showed an upward trend. The upregulation of Gq/11 protein content may change the coupling efficiency of receptors and effectors, causing the inflammatory signal to further expand and exacerbating intestinal damage.
Zhang Li, Clara Abbas, Parhat Abdureim, Liu Chunxi, Anul Galili - "The change of Gq/11 protein content in rat kidney during ARDS" Journal of Xinjiang Medical University 3:218-220 (2005) PFPC Library
==================================================Objective:
To investigate the dynamic changes of Gq/11 protein in kidney during acute respiratory distress syndrome (ARDS).
Methods:
To establish ARDS model in rats by intravenous injection of oleic acid (OA 0.2 ml/Kg -1) though tail vein. The content of Gq/11 were assessed by Western blot.
Results:
MAP and PaO-2 of OA groups decreased (P<0.05 or 0.01), but BUN and Cr content, LDH activity and MDA content of plasma and kidney significantly increased (P< ;0.01). ACE activity of plasma gradually reduced (P<0.01). On the contrary, ACE activity of kidney increased. The content of Gq/11 obviously increased (P<0.05 or 0.01).
Conclusions:
Up regulation of Gq/11 protein content may play a role in renal injury during ARDS.
Zhang Li, Refat Bekchantaif, Wang Na, et al. - "Protective effects of pre-treatment with propofol and the change of Gq/11 protein on rats during acute respiratory distress syndrome" Journal of Xinjiang Medical University 7:714-718 (2011) PFPC Library
===================================================Objective:
To explore the effect and protective effect of propofol pretreatment on multi-organ Gq/11 protein expression in acute respiratory distress syndrome (ARDS) rats.
Methods
24 male Wistar rats were randomly divided into oleic acid group, pretreatment group, and control group. In the oleic acid group, rats were injected with oleic acid 0.2 ml/kg (within 2 min) into the tail vein to replicate the ARDS model. The pretreatment group was infused with propofol 80 mg.kg-1.h-1 through the left jugular vein, and then injected with oleic acid in the same way 30 minutes later. The control group was injected with the same dose of normal saline from the tail vein.
The mean arterial pressure (MABP), blood gas, plasma and lactate dehydrogenase (LDH), malondialdehyde (MDA), angiotensin converting enzyme (ACE) of each organ in each group of rats were measured. Western blotting method was used to detect the Gq/11 protein content of each organ.
Results
The pH and PaO2 of the oleic acid group and the pretreatment group were lower than those of the control group (P<0.05). Compared with the control group, the LDH activity in plasma and lung, brain, heart, kidney, liver, small intestine of the oleic acid group, as well as the heart, kidney, and small intestine of the pretreatment group was significantly increased (P<0.05). The LDH activities in plasma, lung, brain, heart, kidney, and liver of the pretreatment group were lower than those of the oleic acid group (P<0.05).
Compared with the control group, the MDA contents in plasma, lung, brain, heart, kidney, liver, small intestine of the oleic acid group and the plasma, heart, and kidney of the pretreatment group were significantly increased (P<0.05). The MDA content in plasma, lung, brain, heart, kidney, liver, and small intestine of the pretreatment group was lower than that of the oleic acid group (P<0.05).
Compared with the control group, the ACE activities in plasma and lungs of the oleic acid group and the pretreatment group were significantly reduced (P<0.05), while the ACE activities of the kidneys and small intestine were increased (P<0.05). Compared with the oleic acid group, the plasma ACE activity in the pretreatment group increased (P<0.05), and the ACE activity in the lungs and small intestine decreased (P<0.05).
The expression of Gαq/11 protein in the lung, brain, heart, kidney, liver, and small intestine of the oleic acid group and the lung, brain, heart, kidney, and small intestine of the pretreatment group was significantly higher than that of the control group (P<0.05). Compared with the oleic acid group, the Gαq/11 protein expression in the lung, brain, kidney, and liver of the pretreatment group was reduced (P<0.05), but there was no significant difference in the changes in the heart and small intestine (P>0.05).
Conclusion
Propofol pretreatment can reduce the degree of multiple organ damage in ARDS, and its inhibition of high expression changes of Gq/11 protein may be one of its protective pathways.
SEE also:
Mizuno N, Itoh H - "Functions and regulatory mechanisms of Gq-signaling pathways" Neurosignals 17(1):42-54 (2009). doi: 10.1159/000186689
https://karger.com/nsg/article-abstract ... isms-of-Gq
Gonçalves-de-Albuquerque CF, Silva AR, Burth P, Castro-Faria MV, Castro-Faria-Neto HC - "Acute Respiratory Distress Syndrome: Role of Oleic Acid-Triggered Lung Injury and Inflammation" Mediators Inflamm 260465 (2015) doi: 10.1155/2015/260465
https://pubmed.ncbi.nlm.nih.gov/26640323/