槐耳对急性肾损伤后肾纤维化小鼠内质网应激和凋亡的影响  

Effect of Huaier on endoplasmic reticulum stress and apoptosis in mice with renal fibrosis after acute kidney injury

作　　者：赵晶莹[1] 吴玉斌[1] ZHAO Jingying;WU Yubin(Department of Pediatrics Nephrology and Rheumatology,Shengjing Hospital of China Medical University,Shenyang 110004,China)

机构地区：[1]中国医科大学附属盛京医院小儿肾脏风湿免疫科,沈阳110004

出　　处：《中国医科大学学报》2021年第7期632-636,共5页Journal of China Medical University

基　　金：2020年度中国医科大学附属盛京医院院内一般项目(M0484)。

摘　　要：目的探讨槐耳对急性肾损伤(AKI)后肾纤维化小鼠肾功能的作用机制。方法72只雄性C57BL/6小鼠,随机均分为假手术(Sham)组、缺血再灌注损伤(IRI)组和槐耳治疗(IRI+Huaier)组。分别于术后24 h、3 d、7 d、28 d检测各组血清肌酐水平,HE染色检测肾组织形态学改变、Masson染色检测肾组织胶原形成情况,ELISA法检测肾损伤标志物中性粒细胞明胶酶相关脂质运载蛋白(NGAL)水平,Western blotting检测内质网应激相关分子GRP78和CHOP的表达,TUNEL法测定各组凋亡细胞百分比。结果IRI组术后24 h肌酐最高,之后逐渐下降,各时间点肌酐水平均较Sham组升高(均P<0.05);IRI+Huaier组术后7、28 d肌酐水平较IRI组下降(均P<0.05)。术后28 d IRI组肾脏损伤及纤维化程度较Sham组升高(P<0.01),IRI+Huaier组较IRI组肾脏损伤及纤维化程度减轻(P<0.01)。术后28 d IRI组与Sham组比较GRP78、CHOP表达均明显升高(P<0.05),IRI+Huaier组与IRI组比较GRP78、CHOP表达均下降(P<0.05)。IRI组与Sham组比较凋亡细胞明显增加(P<0.05),IRI+Huaier组与IRI组比较细胞凋亡明显减少(P<0.05)。结论槐耳能够改善AKI后肾纤维化小鼠肾功能,延缓肾损伤及肾间质纤维化进程,其机制可能是通过抑制内质网应激和凋亡实现的。Objective To investigate the protective mechanism of Huaier on renal function in mice with renal fibrosis after acute kidney injury(AKI).Methods Seventy two male C57 BL/6 mice were randomly divided into 3 groups:a sham group,an ischemia reperfusion injury(IRI)group,and an IRI+Huaier group.Blood creatinine was measured at 24 h,3 d,7 d,and 28 d after induction of IRI,Histopathological changes in renal tissue were assessed by HE staining,and collagen formation in renal tissue was assessed by Masson staining.Neutrophil gelatinase-associated lipocalin(NGAL)levels were quantitated by ELISA,and GRP78 and CHOP expression in kidneys was measured by Western blotting.Results Blood creatinine was highest in the IRI group 24 h after surgery,then gradually decreased.Levels in the IRI group were elevated at all four time points compared with the sham group.Creatinine levels in the IRI+Huaier group were decreased at days 7 and 28 after surgery compared with the IRI group(P<0.05).Morphological abnormalities and fibrotic changes were observed in the IRI group compared with the sham group(P<0.01),which were significantly ameliorated by treatment with Huaier(P<0.01).Expression of GRP78 and CHOP in the IRI group was significantly increased compared with the sham group,and was decreased in the IRI+Huaier group compared with the IRI group(P<0.05).The number of apoptotic cells in the IRI group was significantly increased compared with the sham group(P<0.05),and Huaier reduced IRI-induced cell apoptosis(P<0.05).Conclusion Huaier shows therapeutic efficacy in restoring renal function and in preventing fibrotic progression after AKI.The protective mechanism may involve inhibiting endoplasmic reticulum stress and apoptosis.

关 键 词：槐耳 急性肾损伤 肾纤维化 小鼠 内质网应激 凋亡 

分 类 号：R692.6[医药卫生—泌尿科学]