南方医科大学学报

南方医科大学学报 ›› 2021, Vol. 41 ›› Issue (7): 1107-1113.doi: 10.12122/j.issn.1673-4254.2021.07.21

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人参皂苷Rh2调控盘状结构域受体1对糖尿病大鼠肾纤维化和细胞凋亡的影响

沈炳香，王法财，周 艺，李 婷，何春远，赵为陈   

  • 出版日期:2021-07-20 发布日期:2021-07-19

Ginsenoside Rh2 inhibits renal fibrosis and renal cell apoptosis in rats with diabetic nephropathy by downregulating discoid domain receptor 1

  • Online:2021-07-20 Published:2021-07-19

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摘要： 目的 分析人参皂苷Rh2（G-Rh2）对糖尿病肾病（DN）大鼠肾纤维化和细胞凋亡的影响及其作用机制。方法 SPF级，雄性，SD大鼠30只，随机分为对照组（Control组）、DN组以及G-Rh2药物干预组。DN和G-Rh2药物干预组大鼠腹腔注射链脲佐菌素构建DN大鼠模型，Control组大鼠给予等量的柠檬酸缓冲溶液注射。待DN大鼠模型构建成功后，G-Rh2药物干预组给予G-Rh2（20 mg·kg-1 ·d-1）连续灌胃12周，Control和DN大鼠给予等量的生理盐水灌胃。HE染色和PAS染色观察大鼠肾组织形态，Masson染色观察大鼠肾组织纤维化程度，TUNEL染色观察肾组织细胞凋亡情况；Western blot检测大鼠肾组织CollagenI、CollagenIII、Cleaved-caspase-3、Bcl-2、DDR1表达水平；免疫组化定位检测肾组织DDR1表达情况。结果 与Control组相比，DN组肾组织纤维化程度加重，细胞凋亡指数升高（P<0.01），CollagenI、CollagenIII、Cleaved-caspase-3、DDR1表达上调（P<0.01），Bcl-2表达下调（P<0.01）；与DN组相比，G-Rh2药物干预组肾组织纤维化程度，细胞凋亡指数，CollagenI、CollagenIII、Cleaved-caspase-3、DDR1表达均显著降低（P<0.05或P<0.01），Bcl-2表达显著升高（P<0.05）。结论 G-Rh2抑制糖DN肾纤维化和细胞凋亡可能与下调DDR1表达有关。

关键词: 糖尿病肾病, 人参皂苷Rh2, 盘状结构域受体1, 肾纤维化, 细胞凋亡

Abstract: Objective To investigate the effect of ginsenoside Rh2 (G-Rh2) on renal fibrosis and cell apoptosis in rats with diabetic nephropathy (DN) and explore its possible mechanism. Methods Thirty male SD rats were randomized equally into control group, DN group and ginsenoside Rh2 intervention group. In the latter two groups, rat models of DN were established by intraperitoneal injection of streptozotocin, and the rats in the control group received injection of citrate buffer. After successful modeling, the rats in ginsenoside Rh2 intervention group were given ginsenoside Rh2 (20 mg · kg- 1) intragastrically on a daily basis for 12 weeks, and those in the other two groups were treated with normal saline. After the treatments, the histological changes of the kidneys of the rats were observed using HE staining and PAS staining, and renal fibrosis was assessed using Masson staining; TUNEL staining was used to observe cell apoptosis in the kidney tissue. Western blotting was performed to detect renal expressions of collagen I, collagen III, cleaved caspase-3, Bcl-2, and DDR1; the localization of DDR1 expression in the kidney tissue was determined using immunohistochemistry. Results Compared with the control rats, the rat models of DN showed obvious renal fibrosis with an increased apoptosis index in the kidneys (P<0.01), where the expressions of collagen I, collagen III, cleaved caspase-3, and DDR1 were all upregulated (P<0.01) and Bcl-2 expression was down-regulated (P<0.01). Treatment with ginsenoside Rh2 significantly reduced the severity of renal fibrosis, lowered the apoptosis index, decreased the expression levels of collagen I, collagen III, cleaved caspase-3, and DDR1 (P<0.05 or P<0.01), and increased the expression of Bcl-2 in the kidney of rats with DN (P<0.05). Conclusion Ginsenoside Rh2 inhibits renal fibrosis and renal cell apoptosis possibly in association with the down-regulation of DDR1 expression in the kidney of rat models of DN.

Key words: diabetic nephropathy, ginsenoside Rh2, discoid domain receptor 1, renal fibrosis, apoptosis