摘要
目的研究对比剂肾病大鼠肾脏中葡萄糖调节蛋白78（GRP78）的表达情况,探讨内质网应激在对比剂肾病发生发展中的作用。方法将56只大鼠随机分为对照组（B组）和模型组（C组）,每组28只。C组大鼠造模当天每隔15min尾静脉先后注射吲哚美辛（INDO,10mg/kg）、N-硝基-L-精氨酸甲酯（L-NAME,10mg/kg）和760g/L泛影葡胺（10mg/kg）;B组大鼠每隔15min尾静脉先后注射与C组等量的INDO、L-NAME和生理盐水。两组分别于造模后12、24、48、72h各处死6只大鼠,观察大鼠一般状况,检测血尿素氮（BUN）、血肌酐（Scr）;苏木精-伊红（HE）染色观察肾脏病理改变,原位末端转移酶标记法（TUNEL）检测肾脏细胞凋亡情况,RT-PCR检测肾脏GRP78mRNA的表达情况;免疫组化和Western blot方法观察肾脏GRP78蛋白表达情况。结果 B组大鼠肾组织无明显病理损伤,肾组织GRP78 mRNA及蛋白几乎无表达,各时间点血BUN、Scr含量无明显差异（P〉0.05）。与B组相比,C组大鼠各时间点病理损伤较严重,肾组织中GRP78 mRNA及蛋白表达均明显升高,且在12h达到高峰,随后有所降低,差异有统计学意义（t=11.74～49.05,P〈0.05）。各时间点C组血BUN、Scr含量均较B组明显升高,且在48h时达到高峰,随后逐渐下降,差异有统计学意义（t=4.03～47.24,P〈0.05）。结论内质网应激可能参与大鼠对比剂肾病的发生发展。
Objective To investigate the expression of GRP78 in contrast-induced nephropathy（CIN）in rats and explore the role of endoplasmic reticulum stress in the occurrence and development of the disease. Methods Fifty-six Wistar rats were evenly randomized to control group and CIN group.On the day of modelling,the rats in CIN group were given caudal-vein injection of indometacin（10mg/kg）,L-NAME（10mg/kg）,760g/L urografin（10mL/kg）every 15 min in succession;those in the control group were given caudal-vein injection of same volume of INDO,L-NAME and normal saline as given in CIN group,15 min,in succession.At 12,24,48,and 72 hours upon completion of the models,six rats were sacrificed each time to observe their general conditions and detect BUN and Scr.HE staining was used to observe the pathological changes of kidney.TUNEL was used to detect the apoptosis of tubular cells.Real-time PCR was used to detect the expression of GRP78 mRNA.Immunohistochemistry and Western-blotting were used to detect the expression of GRP78 protein in kidney. Results No obvious pathologic damages of kidney were noted in the control group,almost no expressions of GRP78 mRNA and GRP78 protein were observed,and BUN and Scr contents in each time point did not differ significantly（P〉0.05）.Compared with the control group,the damages of kidney in CIN group in each time point were more severe,the expressions of GRP78 mRNA and GRP78 protein markedly increased and reached the peak in 12 hours after the operation,and then decreased somewhat（t=11.74-49.05,P〈0.05）,BUN and Scr elevated and peaked in 48 hours after surgery,and then declined gradually（t=4.03-47.24,P〈0.05）. Conclusion Endoplasmic reticulum stress probably involves in the occurrence and development of contrast-induced nephropathy in rats.
出处
《青岛大学医学院学报》
CAS
2015年第5期566-569,共4页
Acta Academiae Medicinae Qingdao Universitatis
基金
青岛市医疗卫生优秀人才培养项目资助(青卫科教字[2014]8号)
关键词
对比剂肾病
内质网应激
葡萄糖调节蛋白78
contrast-induced nephropathy
endoplasmic reticulum stress
glucose-regulated protein78
