亚慢性镉暴露BALB／c小鼠丝裂原活化蛋白激酶信号通路蛋白在肾损伤中的作用

Effects of mitogen-activated protein kinases signaling pathway proteins on kidney injury in mice exposed subchronicaily to cadmium

目的探讨丝裂原活化蛋白激酶（mitogen activated protein kinase，MAPK）和细胞外信号调节激酶（extracellular signal-regulated kinases, ERK）在亚慢性镉染毒小鼠肾脏损害发生后表达的变化及其意义。方法21只雌性BALB／c小鼠随机分成3组，高、低剂量染镉组分别腹腔注射CdCl2溶液10．0、2．5μmol／kg，对照组腹腔注射等量生理盐水，每周3次连续染毒14周。对肾脏进行苏木精-伊红（HE）染色、碘酸雪夫（PAS）染色和胶原纤维染色（Masson染色），观察肾组织病理变化；免疫印迹（Western blot）法检测肾脏中ERK、p38、c—Jun氨基末端激酶（JNK）蛋白及其磷酸化蛋白的表达差异。结果高剂量染镉组pERK、pp38和pJNK蛋白表达水平均高于对照组，差异有统计学意义（P〈0．05），低剂量染镉组pJNK蛋白表达水平高于对照组，差异有统计学意义（P〈0．05）。镉染毒组的bcl-2、bax蛋白表达水平降低，且bcl-2／bax比值低于对照组，差异有统计学意义（P〈0．05）。镉染毒组肾小球和肾小管均有损害。结论CdCl2可能通过调节ERK、JNK和p38蛋白激酶信号相关蛋白表达水平的变化，引发肾脏损害。

Objective To explore the effects of mitogen activated protein kinase （MAPK） and extracellular signal-regulated kinases （ERK） on kidney injury in female BALB/e mice exposed to cadmium. Method Twenty-one female BALB/c mice were randomly divided into 3 groups, i.e. control group, low Cd exposure group （2.5 μmol/kg） and high Cd exposure group （10 μmol/kg） were exposed to normal saline, 2.5, 10μmol/kg Cd, respectively, 3 times a week for 14 weeks. The kidney slice were stained by HE , PAS and Masson staining to obsmwe the morphological changes. The expression levels of pERK, ERK, pp38, p38, pJNK and JNK proteins in kidneys were tested by Western blot assay. Results The ratios of pERK/ERK, pp38/p38, pJNK / JNK in high Cd group were higher than those in the control group （P〈0.05）. The ratio of pERK/ERK in low Cd group was higher than control group （P〈0.05）. The expression levels of bcl-2, bax proteins and the ratio of bcl- 2 to bax in Cd exposure groups decreased significantly, as compared with the control group （P〈0.05）, The impairment of renal glomeruli and tubules were observed in HE, PAS and Masson staining slices of kidneys in mice exposed to Cd. Conclusion CdCl2 may induced renal injury by affecting the expression levels of MAPK.