黄连解毒汤调控SHR内质网应激通路的分子机制研究

高血压是最常见的心血管疾病，具有中医的“热”、“毒”特性，其过程存在内质网应激（ERS）。清热解毒经方黄连解毒汤（HLJDD）对SHR主动脉eNOS/NO下调、Ca2+失衡有矫正作用，并上调miR-322，三者均与ERS有关。在中医阴阳理论指导下和既往研究基础上，我们提出了HLJDD通过改善高血压的ERS起到对高血压病防治的理论假说。因此我们以SHR为模型，利用RT-PCR、WB等分子生物学技术检测HLJDD干预后SHR血管、心脏GRP78、CHOP的蛋白和mRNA变化，检测PDIA6参与的内质网应激IRE1α-XBP1-CHOP10通路相关蛋白、mRNA变化及miR-322、eNOSmRNA变化，并进一步用HLJDD含药血清干预衣霉素诱导的人脐静脉内皮细胞ERS细胞模型进行验证。以明确HLJDD改善高血压病ERS的分子通路及其关联性，对高血压的防治提供更多的实验支持。

Hypertension is the most common cardiovascular disease and has the characteristics of "heat" and "toxic" in traditional Chinese medicine (TCM). There is endoplasmic reticulum stress (ERS) in the process.Qingrejiedu classical prescriptions Huanglian Jiedu Decoction (HLJDD) has a correction effect on eNOS/NO downregulation and Ca2+ imbalance in SHR aorta, and up-regulates miR-322, all of which are related to ERS.Based on the theory of yin and yang in traditional Chinese medicine and previous studies,we proposed that HLJDD could improve the hypertension of ERS to prevent hypertension.Therefore, we used SHR as a model and used RT-PCR, WB and other molecular biology techniques to detect the changes of SHR vascular,cardiac GRP78,and CHOP proteins and mRNA after HLJDD intervention, and to detect the involvement of PDIA6 in endoplasmic reticulum stress IRE1α-XBP1-CHOP10. Pathway-associated proteins, mRNA changes and miR-322, eNOS mRNA changes,and further HLJDD drug-containing serum intervention tunicamycin induced human umbilical vein endothelial cells ERS cell model for validation. In order to provide more experimental support for the prevention and treatment of hypertension, it is necessary to confirm that Huanglian Jiedu Decoction can improve the molecular pathways of ERS in hypertension and its relevance.