钩藤生物碱抑制高血压大鼠主动脉胶原沉积及对基质金属蛋白酶的影响

目的探讨钩藤碱、异钩藤碱和钩藤总生物碱抑制SHR(自发性高血压大鼠(spontaneous hypertension rats,SHR)胸主动脉胶原沉积的实验效应及相关机制。方法 40只SHR随机分为5组:模型组、卡托普利组、异钩藤碱组、钩藤碱组和钩藤总生物碱组;Wistar大鼠8只作为正常对照组。卡托普利组给药量为每天17.5 mg.kg-1,异钩藤碱组、钩藤碱组和钩藤总生物碱组的给药量分别为每天5、5、50 mg.kg-1,模型组和正常组给予等容量生理盐水。灌胃给药8周。取胸主动脉,通过Masson染色法、免疫组织化学染色法、原位杂交法并结合图像分析技术,观察钩藤碱、异钩藤碱和钩藤总生物碱对SHR胸主动脉胶原、ColⅠ、ColⅢ、MMP-9、MMP-2、TIMP-2表达的影响。结果钩藤碱、异钩藤碱和钩藤总生物碱能够降低SHR胸主动脉胶原含量,下调ColⅠ、ColⅢ的蛋白和mRNA表达水平,上调MMP-9和MMP-2蛋白表达水平,上调MMP-9 mRNA表达水平,下调TIMP-2蛋白和mRNA表达水平。结论钩藤碱、异钩藤碱和钩藤总生物碱具有抑制SHR胸主动脉胶原重塑的效应,部分机制与上调MMP-9和MMP-2、下调TIMP-2的表达有关。

Inhibition of Uncaria alkaloids on collagen deposition of SHR thoracic aorta and effects on matrix metalloproteinase

Aim To study the inhibition of rhynchophylline,isorhynchophylline and Uncaria alkaloids on collagen deposition in SHR(spontaneous hypertension rats)thoracic aorta and the related mechanisms.Methods 40 SHR were randomly divided into five groups:model group,captopril group,rhynchophylline group, isorhynchophylline group and total Uncaria alkaloids group,with the 8 Wistar rats as normal control group.Intragastric administrated for 8 weeks,dose:captopril group,17.5 mg·kg-1 body weight per day;isorhynchophylline group and rhynchophylline group,5 mg·kg-1 body weight per day;total Uncaria alkaloids group,50 mg·kg-1 body weight per day;model group and normal control group were given same volume of saline.Thoracic aorta was taken by surgery.Collagen deposition and Col Ⅰ,Col Ⅲ,MMP-9,MMP-2,TIMP-2 expression were observed by Masson staining,immunohistochemistry and in situ hybridization,with image analysistechniques.Results Rhynchophylline,isorhynchophylline and Uncaria alkaloids could reduce the collagen content in SHR thoracic aorta,as well as reduce protein and mRNA levels of Col Ⅰ and Col Ⅲ and increase MMP-9 and MMP-2 protein levels,increase MMP-9 mRNA expression level,and reduce TIMP-2 protein and mRNA expression levels.Conclusions Rhynchophylline,isorhynchophylline and Uncaria alkaloids can inhibit collagen remodeling of the SHR thoracic aorta.Part of the mechanism is the expression increase of MMP-9 and MMP-2,and the expression decrease of TIMP-2.