抑制TRPV4受体对糖尿病大鼠视网膜神经元损伤的影响

Effect of TRPV4 receptor inhibitor on retinal neuron damage in diabetic rats

目的探讨TRPV4受体在糖尿病大鼠视网膜神经元损伤中的作用。方法雄性SD大鼠30只,采用随机数字表法分成对照组、糖尿病组、RN-1734 (TRPV4受体抑制剂)治疗组。后两组采用单次腹腔注射链脲佐菌素(streptozotocin, STZ, 55 mg/kg)诱导糖尿病模型。模型诱导成功后,治疗组给予RN-1734玻璃体内注射给药。12周后,免疫荧光染色检测视网膜生长相关蛋白-43(GAP-43)和突触素(synaptophysin, SYN)表达,Western blot检测GAP-43、SYN和TRPV4相对表达量,HE染色检测视网膜神经节细胞(retinal ganglion cells, RGC)数量。结果与对照组相比,糖尿病组GAP-43、TRPV4表达水平增加,SYN表达水平和RGC数量明显降低;与糖尿病组相比,RN-1734治疗组GAP-43、SYN和RGC数量均明显增加,TRPV4表达明显降低。结论抑制TRPV4受体增加糖尿病大鼠RGC数量,与上调GAP-43和SYN表达水平有关。

Objective To investigate the role of TRPV4 receptor in retinal neuron injury in diabetic rats. Methods Thirty male SD rats were randomly divided into control group, diabetic group and RN-1734(TRPV4 receptor inhibitor) treatment group. In the latter two groups, diabetic models were induced by single intraperitoneal injection(IP) of streptozotocin(STZ, 55 mg/kg). After successful induction of the model, RN-1734 was given by intravitreal injection in the treatment group. 12 weeks later, the expressions of growth-associated protein-43(GAP-43) and synaptophysin(SYN) were detected by immunofluorescence staining, the relative expressions of GAP-43, SYN and TRPV4 were detected by Western blot, and the number of retinal ganglion cells(RGC) was detected by HE staining. Results Compared with the control group, the expression level of GAP-43 and TRPV4 increased, the expression level of SYN and the number of RGC decreased significantly in the diabetic group. Compared with the diabetic group, the expression level of GAP-43 and SYN, and the number of RGC increased significantly, but decreased for TRPV4 expression in RN-1734 treatment group. Conclusion Inhibition of TRPV4 receptor increased the number of RGC in diabetic rats, which is related to up-regulation of the GAP-43 and SYN expression.