内质网应激相关蛋白GADD153/CHOP在系膜增生性肾炎肾组织中的表达及中药干预研究

Expression of Endoplasmic Reticulum Stress Associated Protein GADD153 / CHOP in Nephridial Tissue with Mesangial Proliferative Nephritis and Intervention with Chinese Medicine

目的:研究系膜增生性肾小球肾炎(Ms PGN)大鼠肾脏组织内质网应激相关蛋白生长停滞及DNA损伤基因153(GADD153)/C-EBP同源蛋白(CHOP)的表达、中药保肾颗粒对GADD153/CHOP表达的干预效果,探讨保肾颗粒治疗系膜增生性肾小球肾炎的作用机制。方法:大鼠随机分为中药组、对照组、模型组、空白组,中药组给予保肾颗粒、对照组给予雷公藤多甙片灌胃、空白组和模型组以等量生理盐水灌胃,连续14周。于造模后给药前1 d及实验结束后,检测各组大鼠血清肌酐(SCr),TUNEL检测大鼠肾脏细胞凋亡情况,实时荧光定量聚合酶链反应(Q-PCR)及Western blot法检测肾组织GADD153/CHOP的表达。结果:与模型组比较,对照组和中药组SCr均显著下降(P<0.05)。空白组肾组织细胞凋亡不明显,模型组有大量的肾组织细胞凋亡,中药组及对照组凋亡较轻。与模型组比较,中药组及对照组GADD153/CHOP及GADD153/CHOPmRNA表达水平下降(P<0.05)。结论:Ms PGN大鼠肾组织GADD153/CHOP表达增高,提示内质网应激可能参与了肾脏损害;而保肾颗粒对Ms PGN大鼠肾组织GADD153/CHOP过度表达有较好的抑制作用,且作用与雷公藤多甙片相当,是减轻肾脏损害的重要机制之一。

Objective： to study the expression of GADD153/CHOP （ growth arrest and DNA damage inducible gene 153/E-EBP homologous Protein ） in MsPGN （ mesangial proliferative glomerulonephritis ）, and the intervention of Chinese medicine Baoshen Keli （ Kidney-preservation Granules） , and to explore the functional mechanism in treating MsPGN. Methods ： the rats were randomly divid- ed into Chinese medicine group with Baoshen Keli , control group with Glucosidorum Tripterygll Totorum, model group and blank group with intragastric administration of the same volume of physiological saline, for 14 weeks successively. One day before the administration and after the experiment, detect SCr of each group, detect through TUNEL the nephridial apoptosis and FQ-PCR （ fluorescent quantita- tion polymerase chain reaction）, and detect the GADD153/CHOP expressions through Western blot. Results： compared with model group, SCr in control group and Chinese medicine group were decreased significantly （ P 〈 0. 05 ）. No obvious apoptosis showed in blank group while it was great in model group, and the apoptosis in Chinese medicine group and control group were less. Compared with model group, GADD153/CHOP and GADD153/CHOPmRNA expressions decreased （ P 〈0. 05 ）. Conclusion： The increase of GADD153/CHOP expression of MsPGN rats indicates that the endoplasmic reticulum stress may be involved in kidney damage; Baoshen Keli has a good depressant effect on GADD153/CHOP expressions, equivalent to Glucosidorum Tripterygll Totorum, which may be one of the mechanisms in lessening the kidney damages.