参芍口服液对糖尿病肾病大鼠肾脏内质网应激因子GRP 78、PERK及CHOP表达的影响  

Effect of Shenshao oral liquid on expression of GRP78, PERK and CHOP in rat models of diabetic nephropathy

作　　者：远迪 董云朋 曾招军 黄安静 张春来[2] 周洪霞[2] 

机构地区：[1]华北理工大学,河北唐山063000 [2]河北省唐山工人医院心内四科,河北唐山063000

出　　处：《中国现代医学杂志》2017年第27期22-26,共5页China Journal of Modern Medicine

摘　　要：目的观察参芍口服液对糖尿病肾病大鼠肾脏内质网应激标志性因子GRP78、PERK及CHOP表达的影响。方法将30只健康雄性Wistar大鼠随机分为正常对照组(Sham组)、模型组(DN组)和参芍口服液组(SS组)。DN组和SS组予以高脂饲料加链脲佐菌素腹腔注射复制糖尿病肾病模型。SS组每日1次给予参芍口服液(250 mg/kg)灌胃,Sham组和DN组每日1次给予等剂量的蒸馏水灌胃。12周后检测各组血糖、尿素氮(BUN)、肌酐(Scr)及24 h尿蛋白定量(PRO);HE染色光镜下观察大鼠肾组织病理形态学改变;Western blot检测大鼠肾组织GRP78、PERK及CHOP蛋白表达情况;TUNEL染色检测大鼠肾组织细胞凋亡情况。结果DN组血糖、BUN、Scr及PRO与Sham组相比均增高,SS组血糖、BUN、Scr及PRO与DN组相比均降低(P<0.05)。HE发现Sham组大鼠肾组织形态结构清楚,未见异常;DN组可见肾小球体积增大,可见大量炎症细胞浸润,肾小球系膜基质区增生,肾小管基底膜增厚,部分肾小球、肾小管出现纤维化;SS组肾组织病理形态变化轻于DN组。Western blot发现DN组肾脏组织GRP78、PERK及CHOP蛋白表达高于Sham组,SS组肾组织GRP78、PERK及CHOP蛋白表达均低于DN组(P<0.05)。TUNEL发现DN组较Sham组肾脏组织存在更多细胞凋亡;SS组凋亡细胞少于DN组。结论参芍口服液可减轻糖尿病肾病大鼠肾脏病理损害,延缓肾功能减退,具有肾保护作用,其机制可能与降低内质网应激相关因子GRP78、PERK及CHOP的表达及减少肾组织细胞凋亡有关。Objective To investigate the effect of Shenshao oral liquid on expression of endoplasmicreticulum stress factors GRP78, PERK and CHOP in rat models of diabetic nephropathy. Methods A total of30 healthy male Wistar rats were randomly divided into Sham group, model group （DN group） and Shenshaooral liquid group （SS group）. Animals in DN group and SS group were fed with high fat diet in addition tointraperitoneal injection of streptozotocin. Rats in SS group were administrated with Shenshao oral liquid （250mg/kg） daily, and distilled water were administered daily into rats from Sham group and DN group. Bloodglucose, blood urea nitrogen （BUN）, creatinine （Scr） and 24-hour urinary protein （PRO） were measured 12weeks post insults. Histopathological changes in renal tissue were graded through HE staining. Expressionlevels of GRP78, PERK and CHOP in kidney were measured by Western blot. Apoptosis rate were determinedby TUNEL staining. Results Blood glucose, BUN, Scr and PRO in rats from DN group were significantlyincreased compared with Sham group（ P〈 0.05）, which were attenuated with treatment of Shenshao oral liquid（ P〈 0.05）. HE staining showed that morphological abnormality was observed in DN group including enlargedglomerular volume, inflammatory cell infiltration, glomerular mesangial stromal hyperplasia, tubular basementmembrane thickening, and glomerular and tubular fibrosis. Above histopathological deterioration of renal tissuewas significantly ameliorated by treatment of Shenshao oral liquid （ P〈 0.05）. Western blot showed that theexpression levels of GRP78, PERK and CHOP in renal tissue of DN group were significantly increased whencompared with Sham group, which was decreased in SS group. TUNEL staining manifested that increasedapoptosis rate in DN group （ P〈 0.05） in comparison with Sham group could be attenuated in SS group （ P〈0.05）. Conclusions Shenshao oral liquid reduces development of diabetic nephropathy, restoring renal functionin dependence of man

关 键 词：参芍口服液 糖尿病肾病 内质网应激 细胞凋亡 PERK 大鼠 

分 类 号：R587.2[医药卫生—内分泌]