JNK信号通路在庆大霉素诱导肾损伤大鼠细胞凋亡中的机制及左归丸干预作用研究  

Mechanism of JNK signaling pathway in gentamicin-induced apoptosis of renal injury in rats and intervention effect of Zuoguiwan

作　　者：范为民[1] 王小琴[2] 

机构地区：[1]湖北中医药大学,武汉430061 [2]湖北省中医院,武汉430061

出　　处：《中华中医药杂志》2013年第5期1346-1350,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家临床重点专科建设项目(No.FW20113289)~~

摘　　要：目的:探讨c-Jun氨基末端激酶(JNK)信号通路在庆大霉素诱导肾损伤大鼠细胞凋亡中的机制及左归丸干预效果。方法:将40只雄性Wistar大鼠随机分为空白组(C组)、模型组(M组)、SP600125组(S组)和左归丸组(Z组),各组大鼠连续给予相应药物10d。第11天测量各组大鼠尿N-乙酰-β-D氨基葡萄糖苷(NAG)酶、血肌酐(Scr)、血尿素氮(BUN)等生化指标;以TUNEL方法检测各组大鼠肾脏细胞凋亡情况;以免疫组化技术检测各组大鼠肾脏JNK、p-JNK的表达;以Western Blot方法检测各组大鼠肾脏JNK、p-JNK蛋白的表达。结果:与C组比较,M组的大鼠尿NAG酶、血Scr、血BUN值显著升高(P<0.01);与M组比较,S组和Z组生化指标得到改善,差异具有统计学意义(P<0.05,P<0.01)。与C组比较,M组阳性细胞数目较多,差异具有统计学意义(P<0.01);而S组与Z组阳性细胞数目明显下降,差异具有统计学意义(P<0.01)。与C组比较,M组JNK、p-JNK在肾小管大量表达,差异有统计学意义(P<0.01);与M组比较,S组与Z组蛋白表达较少,差异具有统计学意义(P<0.05,P<0.01)。M组JNK、p-JNK蛋白灰度值较C组明显升高(P<0.01),S组与Z组较模型组灰度值下降(P<0.05,P<0.01)。结论:JNK信号通路在庆大霉素诱导肾损伤大鼠细胞凋亡中起着重要调控机制。左归丸具有与SP600125相同的作用,其机制可能是通过抑制JNK通路的激活,减少细胞凋亡的发生而对庆大霉素诱导肾损伤大鼠起保护作用。Objective： To explore the mechanism of JNK signaling pathway in gentamicin-induced apoptosis of renal injury in rats and intervention effect of Zuoguiwan. Methods： 40 male Wistar rats were divided randomly into control group （C group）, model group （M group）, SP600125 group （S group） and Zuoguiwan group （Z group）. The C group was given intraperitoneal injection of 0.9% saline 2.5mL^-1·kg^-1·d^-1, M group was given intraperitoneal injection of gentamicin sulfate 100mg^-1·kg^-1·d^-1, S group was given intraperitoneal injection of gentamicin sulfate 100mg^-1·kg^-1·d^-1 and intraperitoneal injection of SP600125 15mg^-1·kg^-1·d^-1, Z group was given intrapefitoneal injection of gentamicin sulfate 100mg^-1·kg^-1·d^-1 and gavage Zuoguiwan aqueous solution 2g·200g^-1d^-1. Four groups of rats were administered for 10 consecutive days. After the experiment measuring NAG, Scr and BUN of rat, TUNEL technique was used to detect cell apoptosis of the rat kidney technique was used to detect p-JNK and JNK＇s expression of the rat kidney. Western Blot technique was used to detect p-JNK and JNK＇s protein expression of the rat kidney. Results： The results of biochemical index showed： compared with C group, the rats of M group NAG, Scr and BUN significantly increased （P〈0.01）; compared with M group, the biochemical parameters improved in S group and Z group, with a statistically significant difference （P〈0.05, P〈0.01）. The TUNEL results showed： compared with C group, Apoptosis positive cells of M group was significantly increased, with a statistically significant difference （P〈0.01）; compared with M group, the biochemical parameters of rats improved in S group and Z group, with a statistically significant difference （P〈0.01）. The Immunohistochemical results showed： compared with C group, the rats of M group p-JNK, JNK abundantly expressed in the renal tubules, with a statistically significant difference （P〈0.01）; compared with M group, protein expression was no

关 键 词：庆大霉素 左归丸 SP600125 细胞凋亡 JNK信号通路 肾损伤 

分 类 号：R285.5[医药卫生—中药学]