摘要
目的 探讨马里苷对糖尿病瘦素受体基因缺陷(db/db)小鼠肾脏组织内皮-间质转化(EndMT)和纤维化的改善作用及机制。方法 将10只野生型瘦素受体基因缺陷杂合(db/m)正常雄性小鼠作为正常对照组,将30只db/db小鼠随机分为糖尿病模型组10只、二甲双胍组10只、马里苷组10只。二甲双胍组给予二甲双胍280 mg/kg灌胃、马里苷组给予50 mg/kg马里苷组灌胃,正常对照组、糖尿病模型组给予0.5%羧甲基纤维素钠灌胃,体积均为0.2 mL/10 g,每日1次,共持续8周。第8周末次给药后24 h,检测小鼠空腹血糖;用Western blotting法检测肾组织中EndMT标志物[纤维连接蛋白(Fibronectin)、波形蛋白(Vimentin)、血小板-内皮细胞黏附分子(CD31)]、纤维化指标[转化生长因子β(TGF-β)]、成纤维细胞生长因子受体1(FGFR1)蛋白表达;用RT-PCR法检测肾组织中Fibronectin、CD31、FGFR1 mRNA表达。结果 与正常对照组比较,糖尿病模型组空腹血糖水平高(P<0.05);与糖尿病模型组比较,二甲双胍组、马里苷组空腹血糖水平低(P均<0.05);二甲双胍组空腹血糖水平与马里苷组比较差异无统计学意义(P>0.05)。与正常对照组比较,糖尿病模型组Fibronectin、Vimentin、TGF-β、FGFR1蛋白表达高,CD31蛋白表达低,比较差异有统计学意义(P均<0.05);与糖尿病模型组比较,二甲双胍组、马里苷组Fibronectin、Vimentin、TGF-β、FGFR1蛋白表达低,CD31蛋白表达高,比较差异有统计学意义(P均<0.05);与二甲双胍组比较,马里苷组Vimentin、FGFR1蛋白表达低(P均<0.05),其他蛋白表达比较差异无统计学意义(P均<0.05)。与正常对照组比较,糖尿病模型组Fibronectin、FGFR1 mRNA表达高,CD31 mRNA表达低,比较差异有统计学意义(P均<0.05);与糖尿病模型组比较,二甲双胍组、马里苷组Fibronectin、FGFR1 mRNA表达低,CD31 mRNA表达高,比较差异有统计学意义(P均<0.05);与二甲双胍组比较,马里苷组Fibronectin、CD31 mRNA表达低(P均<0.05),FGFR1 mRNA表达比较差异无统计学意义(P均<0.05)。结论 马里苷可改善db/db小鼠EndMT和纤维化,其机制可能与降低FGFR1表达有关。
Objective To investigate the effect and mechanism of marein on renal endothelial-to-mesenchymal transition(EndMT) and fibrosis in diabetic mice with leptin receptor gene deficiency(db/db). Methods Ten wild-type leptin receptor gene deficiency heterozygous(db/m) male mice were taken as the normal control group, and 30 db/db mice were randomly divided into the diabetic model group(n=10), metformin group(n=10), and marein group(n=10). Mice in the metformin group were given 280 mg/kg metformin, mice in the marein group were given 50 mg/kg marein, and mice in the normal control group and diabetic model group were given 0. 5% sodium carboxymethyl cellulose through intragastric administration, 0. 2 mL/10 g, once a day, for 8 weeks. At the end of the 8th week, fasting blood glucose was measured at 24 h after the last administration. The protein expression levels of EndMT markers [Fibronectin, Vimentin, and plateletendothelial cell adhesion molecule(CD31)], fibrosis markers [transforming growth factor(TGF-β)] and fibroblast growth factor receptor I(FGFR1) in kidney tissues of mice in each group were detected by Western blotting. The mRNA expression levels of Fibronectin, CD31 and FGFR1 were detected by RT-PCR. Results Compared with the normal control group, fasting blood glucose level in the diabetic model group was higher(P<0. 05). Compared with the diabetic model group, fasting blood glucose levels in the metformin group and marein group were lower(all P<0. 05). There was no significant difference in fasting blood glucose level between the metformin group and marein group(P>0. 05). Compared with the normal control group, the protein expression levels of Fibronectin, Vimentin, TGF-β, and FGFR1 were higher in the diabetic model group, and CD31 protein was lower, with statistically significant differences(all P<0. 05). Compared with the diabetic model group, the protein expression levels of Fibronectin, Vimentin, TGF-β, FGFR1 were lower in the metformin group and marein group, while the expression of CD31 protein was higher, with statistically significant differences(all P<0. 05). Compared with the metformin group, the expression levels of Vimentin and FGFR1 proteins in the marein group were lower(all P<0. 05), but there was no significant difference in the expression of other proteins(P>0. 05). Compared with the normal control group, the mRNA expression levels of Fibronectin and FGFR1 were higher in the diabetic model group, while the mRNA expression of CD31 was lower, with statistically significant difference(all P<0. 05).Compared with the diabetic model group, the mRNA expression levels of Fibronectin and FGFR1 in the metformin group and marein group were lower, while the mRNA expression of CD31 was higher, and the differences were statistically significant(all P<0. 05). Compared with the metformin group, the mRNA expression levels of Fibronectin and CD31 in the marein group were lower(all P<0. 05), but there was no significant difference in FGFR1 mRNA expression(P>0. 05). Conclusion Maricin can ameliorate renal EndMT and fibrosis in diabetic db/db mice, and the mechanism may be related to decreased FGFR1 expression.
作者
张芳
郭琼
田亚婷
张博翔
李甜
ZHANG Fang;GUO Qiong;TIAN Yating;ZHANG Boxiang;LI Tian(School of Basic Medical Sciences,Xinjiang Medical University,Urumqi 830011,China;不详)
出处
《山东医药》
CAS
2023年第7期16-20,共5页
Shandong Medical Journal
基金
新疆维吾尔自治区高校科研计划项目(XJEDU2020Y021)
国家级大学生创新创业训练计划项目(202010760011)
新疆维吾尔自治区自然科学基金资助项目(2018D01C181)。
关键词
糖尿病肾病
马里苷
肾脏纤维化
内皮-间质转化
小鼠
diabetic nephropathy
marein
renal fibrosis
endothelial-to-mesenchymal transition
mice