外源性精胺对糖尿病肾病小鼠肾纤维化的影响及其机制

doi:10.12047/j.cjap.5973.2020.046

中国应用生理学杂志 ›› 2020, Vol. 36 ›› Issue (3): 207-210.doi: 10.12047/j.cjap.5973.2020.046

外源性精胺对糖尿病肾病小鼠肾纤维化的影响及其机制

邵小婷¹, 扈敬¹, 张欣颖¹, 赵冰冰¹, 李思葳¹, 高萍², 徐长庆¹, 魏璨^1△

1. 哈尔滨医科大学病理生理学教研室,
2. 附属第二医院, 黑龙江哈尔滨 150086

收稿日期:2019-11-18 修回日期:2020-03-25 发布日期:2020-09-25
通讯作者: Tel: 0451-86674548; E-mail: canwei528@163.com
基金资助:
国家自然科学基金资助项目(81800260);黑龙江省博士后基金(LBH-Z17103)

Effect of exogenous spermine pretreatment on alleviating renal fibrosis in diabetic nephropathy mice and its related mechanism

SHAO Xiao-ting¹, HU Jing¹, ZHANG Xin-ying¹, ZHAO Bing-bing¹, LI Si-wei¹, GAO Ping², XU Chang-qing¹, WEI Can^1△

1. Department of Pathophysiology,
2. Affiliated Second Hospital, Harbin Medical University, Harbin 150086, China

Received:2019-11-18 Revised:2020-03-25 Published:2020-09-25

摘要/Abstract

摘要： 目的: 观察外源性精胺对糖尿病肾病(DN)肾纤维化的保护作用,并探讨其机制。方法: 24 只雄性 C57 小鼠随机分为正常组(Control)、糖尿病组(T1D)和精胺预处理组(T1D+Sp,每组 n=8)。一次性注射 STZ(60 mg/kg)复制 1 型糖尿病小鼠模型,精胺预处理组在 STZ 注射前两周每天腹腔注射精胺(Sp,5 mg/(kg·d)),随后隔天注射精胺,第 12 周处死小鼠,检测血清肌酐、尿素氮判断肾功能变化,HE、PAS 和 Masson 染色观察肾组织损伤和纤维化水平。Western blot 法检测小鼠肾组织中基质金属蛋白酶(MMP-2、MMP-9)、IV型胶原(Coll-IV)蛋白的表达。结果: 与 Control 相比,T1D 组血糖(5.67±0.22 vs 28.40±0.57 mmol/L)、肌酐(14.33±1.22 vs 30.67±4.73 μmol/L)、尿素氮(6.93±4.94 vs 22.00±1.04 mmol/L)明显升高(P＜0.05),肾组织基底膜增厚,胶原含量明显增加,MMP-2、MMP-9 和 Coll-IV 蛋白表达均升高(分别为 0.57±0.07 vs 1.06±0.20、47.00±0.04 vs 1.29±0.09和0.42±0.16 vs 0.95±0.18,P＜0.05),精胺预处理明显减轻上述变化。结论: 外源性精胺预处理通过调节 MMPs 与胶原的平衡减轻 DN 小鼠的肾纤维化。

关键词: 糖尿病肾病, 肾纤维化, 精胺, 基质金属蛋白酶, 胶原, 小鼠

Abstract: Objective: To observe the protective effects of exogenous spermine on renal fibrosis induced by diabetic nephropathy (DN) and to explore its mechanism.Methods: Twenty-four male C57 mice were randomly divided into control group, type 1 diabetes group (TID) and spermine pretreatment group (TID+Sp, n=8 in each group). TID mice were induced by STZ (60 mg/kg), and TID+Sp mice were pretreated with spermine (5 mg/(kg·d)) for 2 weeks before STZ injection. The mice were killed at the 12th week. The renal function was determined by serum creatinine and urea nitrogen. HE, PAS and Masson staining were used to evaluate renal tissue injury and fibrosis. The expressions of matrix metalloproteinase (MMP-2, MMP-9) and collagen IV (Coll-IV) in the kidney of mice were detected by Western blot. Results: Compared with the control group, the blood glucose (5.67±0.22 vs 28.40±0.57 mmol/L), creatinine (14.33±1.22 vs 30.67±4.73 μmol/L) and urea nitrogen (6.93±4.94 vs 22.00±1.04 mmol/L) in the T1D group were increased significantly (P＜0.05), the glomerular basement membrane was thickened, the collagen was significantly increased, the expressions of MMP-2, MMP-9 and Coll-IV protein were increased (0.57±0.07 vs 1.06±0.20, 47.00±0.04 vs 1.29±0.09 and 0.42±0.16 vs 0.95±0.18,P＜0.05). Exogenous spermine significantly alleviates the above-mentioned changes. Conclusion: Exogenous spermine pretreatment could significantly alleviate renal fibrosis in diabetic mice by regulating the balance between MMPs and collagen.

Key words: diabetic nephropathy, renal fibrosis, spermine, MMPs, collagen, mice

中图分类号:

R363

邵小婷, 扈敬, 张欣颖, 赵冰冰, 李思葳, 高萍, 徐长庆, 魏璨. 外源性精胺对糖尿病肾病小鼠肾纤维化的影响及其机制[J]. 中国应用生理学杂志, 2020, 36(3): 207-210.

SHAO Xiao-ting, HU Jing, ZHANG Xin-ying, ZHAO Bing-bing, LI Si-wei, GAO Ping, XU Chang-qing, WEI Can. Effect of exogenous spermine pretreatment on alleviating renal fibrosis in diabetic nephropathy mice and its related mechanism[J]. CJAP, 2020, 36(3): 207-210.

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外源性精胺对糖尿病肾病小鼠肾纤维化的影响及其机制

Effect of exogenous spermine pretreatment on alleviating renal fibrosis in diabetic nephropathy mice and its related mechanism

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