一氧化氮对自发性高血压大鼠外周血T淋巴细胞亚群的影响

Effects of NO on T lymphocyte subsets in peripheral blood of spontaneously hypertensive rats

目的探讨一氧化氮(NO)对调节外周血T淋巴细胞亚群的比值和促炎因子的影响及其对高血压造成的靶器官损伤的作用。方法选取12周龄SHR和WKY大鼠,随机分为WKY组、SHR组和SHR+NO干预组,每组6只,SHR+NO干预组按10μg/(kg·d)腹腔注射硝普钠(NO供体)4周,WKY组和SHR组用等量生理盐水腹腔注射4周。测量尾动脉血压后,采用HE染色法观察脑基底动脉和肾脏病理学改变;流式细胞术检测外周血CD4^+/CD8^+和CD4^+CD25^+T细胞比值;ELISA检测外周血血清肿瘤坏死因子-α(TNF-α)水平。结果与WKY组比较,SHR组大鼠出现脑基底动脉内皮细胞受损、血管壁增厚、肾小球萎缩和炎性细胞浸润,SHR+NO干预组较SHR组大鼠炎性损伤程度减轻;与WKY组比较,SHR组大鼠外周血CD4^+/CD8^+的比值升高(P<0.01),CD4^+CD25^+的比值下降(P<0.01),SHR+NO干预组较SHR组CD4^+/CD8^+的比值降低(P<0.01),CD4^+CD25^+的比值升高(P<0.05);SHR组大鼠血清中TNF-α表达较WKY组升高(P<0.01),SHR+NO干预组较SHR组TNF-α表达降低(P<0.05)。结论 NO通过调节外周血T淋巴细胞亚群的比值,减少促炎因子的释放,进而改善高血压造成的靶器官损伤。

Objective To investigate whether NO can relieve hypertensive cerebrovascular and renal injury by regulating the ratio of peripheral blood T lymphocyte subsets and reducing proinflammatory cytokine release.Methods Twelve week SHR and WKY rats were randomly divided into three groups:WKY group,SHR group and SHR+NO intervention group,with6rats in each group.Rats in SHR+NO intervention group were injected intraperitoneally with sodium nitroprusside according to10μg/(kg·d)for4weeks,while WKY group and SHR group were injected intraperitoneally with an equal amount of saline for4weeks.After measuring the tail artery blood pressure,basilar artery and renal pathological changes were observed by HE staining;the rates of CD4+/CD8+and CD4+CD25+T cells were detected by flow cytometry;and the expression of TNF-αwas detected by ELISA.Results The expressions of CD4+/CD8+and TNF-αin SHR group were significantly higher than those in WKY group(P<0.01)while the rate of CD4+CD25+in SHR group was significantly lower than that in WKY group(P<0.01).The expressions of CD4+/CD8+and TNF-αin SHR+NO intervention group were significantly lower than those in SHR group whereas the rate of CD4+CD25+was significantly higher than that in SHR group(P<0.05).Conclusion NO can improve the target organ damage caused by hypertension by regulating the peripheral blood T lymphocyte subsets ratio and reducing the release of proinflammatory factors.