积雪草对早期糖尿病肾病大鼠TGF-β1表达及相关下游信号的影响

doi:10.12047/j.cjap.5528.2018.018

中国应用生理学杂志 ›› 2018, Vol. 34 ›› Issue (1): 69-73.doi: 10.12047/j.cjap.5528.2018.018

积雪草对早期糖尿病肾病大鼠TGF-β₁表达及相关下游信号的影响

马继伟¹, 王宏天¹, 刘浩飞¹, 丁元², 白继琼³, 张翥¹

1. 河南中医药大学第一附属医院, 郑州 450000;
2. 信阳市中心医院, 河南信阳 464000;
3. 巩义市人民医院, 河南巩义 451200

收稿日期:2016-11-28 修回日期:2017-07-03 出版日期:2018-01-28 发布日期:2018-06-19
通讯作者: 马继伟,Tel:13653835130;E-mail:jiwei193074@126.com E-mail:jiwei193074@126.com
基金资助:
国家自然科学基金（81273950）

Effects of centella asiatica granule on the expression of TGF-β₁ and related down-stream signals in rats with early diabetic nephropathy

MA Ji-wei¹, WANG Hong-tian¹, LIU Hao-fei¹, DING Yuan², BAI Ji-qiong³, ZHANG Zhu¹

1. Department of Nephrology, Henan University of Traditional Chinese Medicine Affiliated the First Hospital, Zhengzhou 450000;
2. Xinyang Central Hospital, Xinyang 464000;
3. Gongyi City People's Hospital, Gongyi 451200, China

Received:2016-11-28 Revised:2017-07-03 Online:2018-01-28 Published:2018-06-19
Supported by:
国家自然科学基金（81273950）

摘要/Abstract

摘要： 目的：通过研究积雪草（CA）对早期糖尿病肾病大鼠转化生长因子β₁（TGF-β₁）表达及相关下游信号的影响，阐明积雪草防治早期糖尿病肾病（DN）的分子机制。方法：60只雄性SD大鼠，按体重随机分为假手术组（n=10）和造模组（n=50）。造模组大鼠进行右肾切除术，1周后给以腹腔注射链脲佐菌素（STZ）30 mg/kg，连续给3 d；72 h后测血糖，以 ≥ 16.7 mmol/L，尿糖+++以上及尿量大于对照组的50%为DN模型成模标准。假手术组进行右肾被膜损伤，并注射相应量生理盐水。造模组通过灌胃给药，分为：DN模型组（模型组）、DN+福辛普利组（蒙组1.6 mg/kg·d）、DN+积雪草高剂量组（高剂量组16.8 mg/kg·d）、DN+积雪草中剂量组（中剂量组11.2 mg/kg·d）和DN+积雪草低剂量组（低剂量组5.6 mg/kg·d）（n=10），连续给药16周，每日上午1次灌胃。利用实时荧光定量PCR和Western blot分别检测肾组织中TGF-β₁、TβR1、TβR2、Smad2/3、p-Smad2/3及Smad7 mRNA和蛋白的表达。结果：与假手术组相比，DN组TGF-β₁、TβR1、TβR2、Smad2/3 mRNA和蛋白表达及Smad2/3蛋白的磷酸化水平显著增加（P<0.05）、Smad7 mRNA和蛋白表达明显减少（P<0.05），而福辛普利和高剂量积雪草能倒转DN引起的TGF-β₁、TβR1、TβR2、Smad2/3 mRNA和蛋白表达增加（P<0.05）及Smad7 mRNA和蛋白表达降低（P<0.05）。结论：积雪草可能通过调控TGF-β₁/Smad信号通路起到防治DN的作用。

关键词: 糖尿病肾病, 积雪草, 转化生长因子-β₁, Smad信号通路, 大鼠

Abstract: Objective: To investigate the effects of centella asiatica (CA) granule on the expression of transform growth factor-β₁(TGF-β₁) and related down-stream signals in rats with early diabetic nephropathy(DN) and to clarify the molecular mechanisms of CA molecular mechanism of on preventing and curing early diabetic kidney disease DN by studying the effects of centella asiatica on TGF-β₁ expression and related down-stream signals.Methods: Sixty male SD rats were divided into control group(n=10) and DN model group(n=50). The model rats were made a right nephrectomy. One week later, diabetic nephropathy was induced by intraperitoneal injection of streptocozin(30 mg/kg) for three consecutive days. High blood glucose level of Tail vein (fasting glucose ≥ 16.7 mmol/L) and high urinary protein level(total protein level in DN group was more than twice higher than the control group) were measured to confirm early DN in rats. In the sham operation group, the right renal capsule was damaged and the corresponding amount of saline was injected. The model rats were administrated by the means of intragastric administration. The DN model group were divided into DN group, DN+fosinopril group(1.6 mg/kg·d), DN+high CA group(16.8 mg/kg·d), DN+medium CA group(11.2 mg/kg·d) and DN+low CA group(5.6 mg/kg·d), and each group was intragastric administration one time every morning last for 16 weeks. The expressions of mRNA and protein of TGF-β₁, TβR1, TβR2, Smad2/3, Smad7 and the level of Smad2/3 phosphorylation were detected by using real time quantitative polymerase chain reaction and Western blot.Results: The expressions of mRNA and protein of TGF-β₁, TβR1, TβR2, Smad2/3 and the level of Smad2/3 phosphorylation were significantly increased, the expressions of mRNA and protein of Smad7 were dramatically decreased. The fosinopril and high dosage CA could reverse the effects of DN.Conclusion: CA plays an important role in preventing and curing DN through regulating the TGF-β₁/Smad signaling pathways.

Key words: diabetic nephropathy, centella asiatica, transforming growth factor-beta 1, smad signaling pathway, rat

马继伟, 王宏天, 刘浩飞, 丁元, 白继琼, 张翥. 积雪草对早期糖尿病肾病大鼠TGF-β₁表达及相关下游信号的影响[J]. 中国应用生理学杂志, 2018, 34(1): 69-73.

MA Ji-wei, WANG Hong-tian, LIU Hao-fei, DING Yuan, BAI Ji-qiong, ZHANG Zhu. Effects of centella asiatica granule on the expression of TGF-β₁ and related down-stream signals in rats with early diabetic nephropathy[J]. CJAP, 2018, 34(1): 69-73.

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积雪草对早期糖尿病肾病大鼠TGF-β₁表达及相关下游信号的影响

Effects of centella asiatica granule on the expression of TGF-β₁ and related down-stream signals in rats with early diabetic nephropathy

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