Abstract：【Objective】 To investigate the protective effect of transient receptor potential vanilloid subtype 4 (TRPV4) on cerebral ischemia-reperfusion (I/R) injury in rats,and to explore related mechanisms. 【Methods】 A total of 72 rats were randomly divided into the sham group,the I/R group,the 4-α-phorbol-12,13-didecanoic acid (4α-PDD) group,and the LY294002 group,with 18 rats in each group. At 30 minutes point before modeling,the 4α-PDD group was injected with 4α-PDD 0.2 mg/kg through the tail vein,the LY294002 group was injected with 4α-PDD 0.2 mg/kg and LY294002 0.5 mg/kg,while the sham group and the I/R group,was injected with an equal volume of normal saline into the tail vein. All pretreatments were one-time medications. The nerve function at 24 h after I/R were detected. The cerebral infarct volume was measured as well. The diastolic function of the isolated cerebral basilar artery (CBA) was evaluated. The expressions of protein kinase B (AKT),p-AKT,endothelial nitric oxide synthase (eNOS) and p-eNOS in brain tissue were detected by western blotting. 【Results】 Compared to the I/R group,the nerve function score and cerebral infarction volume decreased in the 4α-PDD group(P<0.05).While compared to the 4α-PDD group,the nerve function score and cerebral infarction volume increased in the LY294002 group (P<0.05).Then,compared with the sham group, the CBA diastolic rate in the I/R group increased (P<0.05); While the CBA diastolic rate increased in the 4α-PDD group (P<0.05) if it was compared with that in the I/R group,However,compared with the 4α-PDD group,the CBA diastolic rate decreased in the LY294002 group (P<0.05).The result of HE staining showed that the hippocampal neuronal nucleoli in the sham group were clear,uniform color,less chromatin,neat arrangement in rows,and oval or round shape in cell body;while the I/R group had large deformation and necrosis of neurons,plus condensed,solid dye,and disorderly arranged nucleuses. However,compared to the I/R group,the number of neurons and the degree of neuronal necrosis in both the 4α-PDD and LY294002 groups got improved where the improvement of the 4α-PDD group was better than that of the LY294002 group. Finally,compared to the sham group,the p-AKT/AKT and p-eNOS/eNOS in the I/R group increased (P<0.05); And compared to the I/R group,the 4α-PDD group had higher levels of AKT/AKT and p-eNOS/eNOS (P<0.05).Furthermore,compared with the 4α-PDD group,the LY294002 group had lower levels of both p-AKT/AKT and p-eNOS/eNOS (P<0.05).【Conclusion】 TRPV4 agonist can improve neurological function and hippocampal pathological changes in I/R brain of rats,promote CBA relaxation,and reduce cerebral infarction volume,which may be achieved by activating the PI3K/AKT/eNOS pathway.
高海茸, 郝艳. TRPV4激动剂对大鼠脑缺血再灌注损伤的保护作用及对PI3K/AKT/eNOS通路的影响[J]. 医学临床研究, 2023, 40(3): 344-347.
GAO Hai-rong, HAO Yan. Protective Effect of TRPV4 Agonist on Cerebral Ischemia-reperfusion Injury in Rats and its Influence on PI3K/AKT/eNOS Pathway. JOURNAL OF CLINICAL RESEARCH, 2023, 40(3): 344-347.
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