中文摘要：

[目的]探讨人肾近曲小管上皮细胞在镉（Cd Cl2）染毒下的信号通路蛋白磷酸化变化及缝隙连接蛋白43（Cx43）的作用。[方法]选取人肾近曲小管上皮细胞系HK-2,给予1μmol/L浓度的Cd Cl2染毒10 d。采用RNA干扰（si RNA）下调Cx43表达,采用Western blot检测Cx43蛋白表达,采用蛋白磷酸化芯片分析细胞信号通路蛋白磷酸化改变。[结果]在Cd Cl2染毒HK-2细胞10 d后,蛋白磷酸化发生变化的位点有61个,发生蛋白磷酸化改变的通路有Erb B、丝裂原活化蛋白激酶（MAPK）、T细胞受体以及B细胞受体信号通路,细胞增殖下降（P〈0.05）,凋亡上升（P〈0.05）;在未染毒时沉默Cx43后,相对于Cx43未沉默组,有56个磷酸化位点发生改变,发生蛋白磷酸化改变的通路有焦点黏连、Erb B、MAPK信号通路等,细胞增殖下降（P〈0.05）,而细胞凋亡未发生变化（P〉0.05）;而染毒后再短暂下调Cx43,相较于镉染毒组,有102个位点变化,而焦点黏连、Erb B、MAPK、凋亡和趋化因子信号通路相关蛋白磷酸化水平发生变化,细胞增殖未发生变化（P〉0.05）,而细胞凋亡下降（P〈0.05）。[结论]镉较长时间染毒HK-2细胞,可能会影响Erb B、MAPK、T细胞及B细胞受体信号通路,抑制细胞增殖,增加细胞凋亡;Cx43表达下降可能会通过改变焦点黏连、Erb B、MAPK、凋亡和趋化因子等信号通路的蛋白磷酸化水平,对细胞增殖与凋亡进行调控。

英文摘要：

[Objective] To investigate the alteration of protein phosphorylation of signaling pathways and the role of connexin 43（Cx43） in human renal proximal tubular cells following cadmium（Cd Cl2） treatment. [Methods] Human renal proximal tubular cell lines（HK-2） were exposed to 1 μmol/L Cd Cl2 for 10 days. Cx43 was silenced by RNA interference technique（si RNA）. Western blot was used to detect protein expression of Cx43. The protein phosphorylation of signaling pathways was determined by phosphor explorer antibody array. [Results] After HK-2 cells exposed to Cd Cl2 for 10 days, 61 phosphorylation proteins were altered, belonging to Erb B, mitogen-activated protein kinase（MAPK）, T cells receptor, and B cells receptor signaling pathways. Decreased proliferation（P〈0.05） and elevated apoptosis（P〈0.05） in HK-2 cells were observed. After Cx43 was silenced prior to the exposure, 56 phosphorylation proteins were altered when compared with the control group, which belonged to Focal adhesion, Erb B, and MAPK signaling pathways. However, apoptosis did not change（P〉0.05） with decreased cell proliferation（P〈0.05）. Compared with the Cd Cl2 exposure group, 102 altered phosphorylation proteins involved in Focal adhesion, Erb B, MAPK, Apoptosis, and Chemokine signaling pathways were identified with decreased apoptosis（P〈0.05） and no change in cell proliferation（P〉0.05） in the Cx43 silencing posterior to Cd Cl2 exposure group. [Conclusion] An extended cadmium exposure of HK-2 cells could decrease cell proliferation, increase apoptosis, and affect Erb B, MAPK, T cells receptor, and B cells receptor signaling pathways. Down-regulated expression of Cx43 may regulate the proliferation and apoptosis of cells by changing the protein phosphorylation of signaling pathways such as Focal adhesion, Erb B, MAPK, Apoptosis, and Chemokine.