首页|活血利水复方对自发性高血压大鼠转化生长因子-β1/SMAD家族蛋白信号通路介导下游结缔组织生长因子及Ⅰ、Ⅲ型胶原表达及血管重塑的影响

活血利水复方对自发性高血压大鼠转化生长因子-β1/SMAD家族蛋白信号通路介导下游结缔组织生长因子及Ⅰ、Ⅲ型胶原表达及血管重塑的影响

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目的:基于转化生长因子-β1/SMAD家族蛋白信号通路探讨活血利水中药复方对自发性高血压大鼠血管重塑的保护作用及机制.方法:将自发性高血压大鼠随机分为模型组、卡托普利组、活血利水复方低剂量组、活血利水复方中剂量组、活血利水复方高剂量组,Wistar大鼠作为空白组,每组10只.给予相应药物灌胃,4周后采用酶联免疫吸附试验方法检测血清中C反应蛋白、肿瘤坏死因子-α、白细胞介素-6的含量;采用逆转录聚合酶链反应检测大鼠主动脉组织转化生长因子-β1、结缔组织生长因子及 Ⅰ型胶原、Ⅲ型胶原mRNA表达,并取冠状动脉组织进行马松三色染色.结果:与空白组比较,模型组血清中C反应蛋白、肿瘤坏死因子-α、白细胞介素-6的含量显著升高(P<0.01);与模型组比较,各药物组大鼠干预后血清中C反应蛋白、肿瘤坏死因子-α、白细胞介素-6的含量不同程度降低(P<0.01).其中,卡托普利组和活血利水复方高剂量组上述3项指标表达最低,与其他组的差异有统计学意义(P<0.05或P<0.01);卡托普利组和活血利水复方高剂量组比较,差异无统计学意义(P>0.05).与空白组比较,模型组大鼠主动脉转化生长因子-β1、结缔组织生长因子及Ⅰ型胶原、Ⅲ型胶原mRNA表达显著升高(P<0.01);与模型组比较,卡托普利组及活血利水复方低剂量组、活血利水复方中剂量组、活血利水复方高剂量组大鼠主动脉组织转化生长因子-β1、结缔组织生长因子及 Ⅰ型胶原、Ⅲ型胶原mRNA表达不同程度降低(P<0.05或P<0.01).结论:活血利水中药复方可通过调控转化生长因子-β1/SMAD家族蛋白信号通路及下游结缔组织生长因子及 Ⅰ型胶原、Ⅲ型胶原mRNA表达水平,降低C反应蛋白、肿瘤坏死因子-α、白细胞介素-6等炎症因子的表达,抑制炎症反应,从而改善高血压病炎症状态及血管重塑,其机制可能与降低转化生长因子-β1、结缔组织生长因子及Ⅰ型胶原、Ⅲ型胶原蛋白沉积有关.
Effects of the Huoxue Lishui prescription on TGF-β1/Smads signaling pathway downstream CTGF,type Ⅰ and Ⅲ collagen expression and vascular remodeling in rats with spontaneous hypertension
Objective:To investigate the protective effect and mechanism of compound prescription of stimulating blood circulation to diuresis on vascular remodeling in spontaneously hypertensive rats(SHR)based on TGF-β1/Smads signaling pathway.Methods:SHR were randomly divided into the model group,the Captopril group,the low dose group of compound prescription of stimulating blood circulation to diuresis,the middle dose group of compound prescription of stimulating blood circulation to diuresis,and the high dose group of compound prescription of stimulating blood circulation to diuresis,and Wistar rats as the blank group,with 10 rats in each group.After intragastric administration of corresponding drugs,the content of CRP,TNF-α,and IL-6 in serum were detected by ELISA in 4 weeks later.The mRNA expression of TGF-β1,CTGF,I collagen and Ⅲ collagen in rat aorta was detected by RT-PCR,and the coronary tissue was subjected to Masson's trichrome staining.Results:Compared with the blank group,the contents of CRP,TNF-α and IL-6 in serum in the model group were significantly increased(P<0.01).Compared with the model group,the levels of CRP,TNF-α and IL-6 in serum of rats in all drug groups were decreased to different degrees(P<0.01).The expression in the Captopril group and the high dose group of compound prescription of stimulating blood circulation to diuresis was the lowest,and the difference was statistically significant compared with other groups(P<0.05 or P<0.01).There was no significant difference between the Captopril group and the high dose group of compound prescription of stimulating blood circulation to diuresis(P>0.05).Compared with the blank group,mRNA expressions of TGF-β1,CTGF,type Ⅰ collagen and type Ⅲ collagen in aorta of rats in the model group were significantly increased(P<0.0l).Compared with the model group,the mRNA expression of TGF-β1,CTGF,and type Ⅰ collagen and Ⅲ collagen in the aorta of rats in the Captopril group,the low dose group of compound prescription of stimulating blood circulation to diuresis,the middle dose group of compound prescription of stimulating blood circulation to diuresis,and the high dose group of compound prescription of stimulating blood circulation to diuresis were decreased to varying degrees(P<0.05 or P<0.01).Conclusion:By regulating the TGF-β1/Smads signaling pathway and the mRNA expression levels of downstream CTGF,and type Ⅰ collagen and type Ⅲ collagen,compound prescription of stimulating blood circulation to diuresis can reduce the expression of CRP,TNF-α,IL-6 and other inflammatory factors to inhibit the inflammatory response,thereby ameliorating the inflammatory state and vascular remodeling of hypertension.The mechanism may be related to the reduction of TGF-β1,CTGF,type Ⅰcollagen and type Ⅲ collagen deposition.

The Huoxue Lishui prescriptionSpontaneously hypertensive ratTransforming growth factor-β1/Smads signaling pathwayVascular remodeling

莫霄云、刘丽云、黄琛、廖博、林良广

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广西中医药大学第一附属医院,广西 南宁,530022

广西中医药大学,广西 南宁,530299

活血利水中药复方 自发性高血压大鼠 转化生长因子-β1/SMAD家族蛋白信号通路 血管重塑

国家自然科学基金地区科学基金项目全国名老中医药专家钱海凌传承工作室

81960850

2024

中医临床研究
中华中医药学会

中医临床研究

影响因子:0.839
ISSN:1674-7860
年,卷(期):2024.16(17)