| Objective: Through Meta-analysis,the clinical efficacy and safety of Gouteng Recipe in the treatment of hypertension were systematically evaluated.From the perspective of the NLRP3 inflammasome,endothelial injury in hypertensive rats and cell models has been studied,and the mechanism of NLRP3 inflammasome-vascular endothelial function injury was explored.At the same time,the intervention effects of Uncaria,Semen Raphani and their component drugs were studied.It also provides a new direction for the treatment of hypertension with traditional Chinese medicine and the protection of vascular endothelial function.Methods:1.By searching the databases of ‘Pubmed’,‘Embase’,‘China Knowledge Infrastructure’,‘Wanfang’,and ‘VIP’,the literatures of randomized controlled trials of Gouteng Recipe in the treatment of hypertension were included.Cochrane Reviewers Handbook 5.1.0 was used for risk of bias assessment.Meta-analysis was then performed using Rev Man 5.3 software.Finally,the clinical efficacy of Gouteng Recipe in the treatment of hypertension were systematically evaluated.2.NLRP3 inflammasome-mediated impairment of vascular endothelial function in SHR: SHR was used as a model of hypertension.NLRP3 gene expression is perturbed in vivo in SHR rats through adeno-associated viruses(AAVs).And the effects on NLRP3 inflammasome,in vivo inflammatory level,and vascular endothelial function were observed by Westernblot,q PCR,and ELISA.3.Uncaria and Semen Raphani and their components intervene vascular endothelial function in SHR: On the basis of previous studies,SHR rats were treated with sinapine thiocyanate,isorhynchophylline,their compatibility,Tengfujiangya tablets,and Diovan.By Westernblot,q PCR,Elisa and other methods,their effects on blood pressure,expression of NLRP3 inflammasome,vascular inflammation level,and endothelial function in SHR rats were observed.4.Effects of Uncaria and Semen Raphani and their components on endothelial function of HUVECs: HUVECs were intervened with Ang II,and the optimal injury concentration of Ang II and the protective concentration of component drugs were screened by MTT assay.The expression of NLRP3 inflammasome,cellular endothelial function and cellular inflammation in vitro were detected by Western blot,q PCR and ELISA,respectively,and the function of cell adhesion,migration and tube formation was detected.Results:1.A total of 22 RCTs were included,with a total of 2900 patients in two groups.The results of this systematic review showed that the treatment group had better antihypertensive effect on systolic blood pressure and diastolic blood pressure compared with the control group,and the difference had statistical significance.2.In SHR rats,impairment of endothelial function,elevated NLRP3 inflammasome expression,and hyperactive inflammatory levels coexist.The results of adeno-associated virus transfection experiments showed that: After the expression of NLRP3 gene was disturbed,NLRP3 and Caspase-1 were decreased at the protein and m RNA expression levels,which indicated that the activation of NLRP3 inflammasome was inhibited to some extent.At the same time,the expression levels of inflammatory level indicators(IL-18,IL-1β)were decreased and the expression of endothelial function indicators(ET-1,NO)was regulated in SHR rats,which indicated that both inflammatory level and endothelial function were improved in SHR rats.3.SHR rats were used as a hypertensive intraductal injury model,and NLRP3 inflammasome activation,hyperactive inflammatory response,and significantly impaired endothelial function were found in SHR rats.After the intervention of Uncaria and Semen Raphani and their components in SHR rats,it was found that the blood pressure of SHR was reduced to different extents,and the expression of NLRP3,caspase-1 protein and m RNA in their aortas was improved,and the activation of NLRP3 inflammasome was inhibited to a certain extent,while the inflammatory response of NF-κB,IL-18,and IL-1βin vivo was alleviated,the expression of endothelial function indicators(e NOS,NO,ET-1)was regulated,and the inflammatory level and endothelial function of SHR rats were improved through the intervention of sinapine thiocyanate,isorhynchophylline,their compatibility,Tengfujiangya tablets,and Diovan.4.After intervention of HUVECs with Ang II,not only NLRP3 inflammasome activation in HUVECs was promoted,but also the downstream inflammatory response was further enhanced,but also e NOS and NO levels in HUVECS were decreased,ET-1 levels were increased,and led to dysfunction of HUVECs migration,adhesion,and tube formation.Sinapine thiocyanate,isorhynchophylline and their combination can significantly reduce the expression levels of NLRP3,caspase-1 protein and m RNA in HUVECs and improve the expression of NF-κB,an indicator of inflammation,adjust the expression of endothelial function indicators(e NOS,NO,ET-1),and improve the migration,adhesion,and tube formation function of HUVECs.This indicates that sinapine thiocyanate,isorhynchophylline,and their combination can inhibit the activation of NLRP3 inflammasome in HUVECs to some extent and improve the inflammatory level and endothelial function of HUVECs.Conclusions: The antihypertensive effect and clinical efficacy of Gouteng Recipe in the treatment of hypertension are significant.NLRP3 inflammasome activation is one of the mechanisms of hypertensive vascular endothelial injury,Uncaria and Semen Raphani can effectively protect hypertensive vascular endothelial function injury,and its effective components isorhynchophylline,sinapine thiocyanate and their combination can reduce the expression of NLRP3 inflammasome to a certain extent,inhibit the hyperactive level of inflammation,and further protect endothelial function. |
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