Wu Yu-Jie, Wang Zhi-Bo, Li Ying, Wang Dao-Ping, Miao Lan, Ren Jun-Guo, Pan Ying-Hong, Liu Jian-Xun
Graduate School, Beijing University of Chinese Medicine Beijing 100029, China Institute of Basic Medical Science, Xiyuan Hospital, China Academy of Chinese Medical Sciences Beijing 100091, China.
Institute of Basic Medical Science, Xiyuan Hospital, China Academy of Chinese Medical Sciences Beijing 100091, China Institute of Crop Science, Chinese Academy of Agricultural Sciences Beijing 100081, China.
Zhongguo Zhong Yao Za Zhi. 2021 Oct;46(19):5052-5063. doi: 10.19540/j.cnki.cjcmm.20210603.402.
Compound Renshen Buqi Granules have been widely used to treat chronic heart failure(CHF) due to Qi deficiency and blood stasis, but the mechanism of action remains unclear. This paper explored the pathogenesis of CHF due to Qi deficiency and blood stasis and the intervention mechanism of Compound Renshen Buqi Granules based on quantitative proteomics for uncovering the biological basis. SD rats were divided into the normal control(N) group, normal+Compound Renshen Buqi Granules(ND) group, model(M) group, model+Compound Renshen Buqi Granules(D) group, and positive control(Y) group. The rat model of CHF due to Qi deficiency and blood stasis was established by ligation of the left anterior descending(LAD) coronary artery and chronic sleep deprivation. The rats in the ND group and D group were provided with Compound Renshen Buqi Granules, while those in the Y group received valsartan. Six weeks later, the serum was sampled and the data-dependent acquisition(DDA) was employed for the non-targeted quantitative proteomics analysis of the differences in protein expression among groups, followed by the targeted analysis of differentially expressed proteins(DEPs) generated by data-independent acquisition(DIA). Compared with the N group, the rats in the M group pre-sented with decreased body weight, grip strength, and pulse amplitude and increased RGB value on the tongue surface. The pathomorphological examination revealed inflammatory cell infiltration, cell degeneration and necrosis, tissue fibrosis, etc. After the intervention with Compound Renshen Buqi Granules, multiple indicators were reversed. As demonstrated by proteomics results, there were 144 and 111 DEPs found in the M group and ND group in comparison with the N group. Compared with the M group, 107 and 194 DEPs were found in the D group and the Y group, respectively. Compared with the ND group, 119 DEPs were detected in the D group. As illustrated by DIA-based verification, the quantitative results of six proteins in each group were consistent with those by DDA. The syndrome indicators and pathomorphological examination results demonstrated that the protein expression profile of rats with CHF due to Qi deficiency and blood stasis changed obviously. However, Compound Renshen Buqi Granules were able to reverse the differential expression of immune proteins to regulate CHF of Qi deficiency and blood stasis syndrome, which has provided clues for figuring out the pathogenesis of CHF due to Qi deficiency and blood stasis and the intervention mechanism of Compound Renshen Buqi Granules.
复方人参补气颗粒已被广泛用于治疗气虚血瘀型慢性心力衰竭(CHF),但其作用机制尚不清楚。本文基于定量蛋白质组学探讨气虚血瘀型CHF的发病机制及复方人参补气颗粒的干预机制,以揭示其生物学基础。将SD大鼠分为正常对照组(N组)、正常+复方人参补气颗粒组(ND组)、模型组(M组)、模型+复方人参补气颗粒组(D组)和阳性对照组(Y组)。采用结扎左冠状动脉前降支(LAD)并结合慢性睡眠剥夺的方法建立气虚血瘀型CHF大鼠模型。ND组和D组大鼠给予复方人参补气颗粒,Y组大鼠给予缬沙坦。6周后采集血清,采用数据依赖采集(DDA)方法对各组蛋白质表达差异进行非靶向定量蛋白质组学分析,随后采用数据非依赖采集(DIA)方法对差异表达蛋白(DEP)进行靶向分析。与N组相比,M组大鼠体重、握力、脉搏幅度降低,舌面RGB值升高。病理形态学检查显示有炎性细胞浸润、细胞变性坏死、组织纤维化等。给予复方人参补气颗粒干预后,多项指标得到逆转。蛋白质组学结果显示,与N组相比,M组和ND组分别有144个和111个DEP。与M组相比,D组和Y组分别有107个和194个DEP。与ND组相比,D组有119个DEP。基于DIA的验证结果表明,各组6种蛋白质的定量结果与DDA结果一致。证候指标和病理形态学检查结果表明,气虚血瘀型CHF大鼠的蛋白质表达谱发生了明显变化。然而,复方人参补气颗粒能够逆转免疫蛋白的差异表达,从而调节气虚血瘀证CHF,为阐明气虚血瘀型CHF的发病机制及复方人参补气颗粒的干预机制提供了线索。