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。

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

赵晶莹, 吴玉斌

中国医科大学附属盛京医院小儿肾脏风湿免疫科, 沈阳 110004

收稿日期:2020-11-13出版日期:2021-07-30发布日期:2021-06-24
通讯作者:吴玉斌E-mail:wuyb@sj-hospital.org
作者简介:赵晶莹(1986-),女,主治医师,博士.
基金资助:2020年度中国医科大学附属盛京医院院内一般项目（M0484）


关键词: 槐耳, 急性肾损伤, 肾纤维化, 小鼠, 内质网应激, 凋亡
Abstract: 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 C57BL/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.
Key words: Huaier, acute kidney injury, renal fibrosis, mice, endoplasmic reticulum stress, apoptosis
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