Qiu Qi, Cao Jinglin, Wang Yong, Zhang Yunnan, Wei Yun, Hao Xiaoyan, Mu Yu, Lin Yang
Department of Pharmacy, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
Lifescience School, Beijing University of Chinese Medicine, Beijing, China.
Front Pharmacol. 2019 Oct 23;10:1267. doi: 10.3389/fphar.2019.01267. eCollection 2019.
This study aimed to investigate the therapeutic effect of traditional Chinese medicine-Buxin Yishen decoction (BXYS) on type 2 cardiorenal syndrome (CRS) caused by myocardial infarction and explore the possible mechanism BXYS works. A chronic heart failure (CHF) rat model induced by left anterior descending coronary artery ligation was used and five groups were created that included a sham group, a CHF model group, a fosinopril group, a BXYS (0.4 g/kg) group and a BXYS (0.8 g/kg) group. Heart function, renal hemodynamics, neuroendocrine factors, serum, and urine concentration of soluble form connective tissue growth factor (sCTGF), expression of CTGF mRNA, CTGF, α-smooth muscle actin (α-SMA), and low-density lipoprotein receptor-related protein (LRP) in renal tissues were evaluated after 28 days and 60 days of drug administration. Histological analysis of kidney tissues was also performed. experiments were designed to verify the results of experiments by detecting factors including CTGF, α-SMA, in NRK-52E cells. Rats with CHF showed obvious pathophysiological changes including: altered renal hemodynamic parameters; dysregulated heart function; changes to serum concentrations of angiotensin II (AngII), cyclic guanosine monophosphate (cGMP), serum creatinine (Scr), blood urea nitrogen (BUN), C-reactive protein (CRP), brain natriuretic peptide (BNP); high serum and urine sCTGF concentration; high CTGF mRNA, CTGF, α-SMA and LRP expression in renal tissues; increased extracellular matrix (ECM) deposition and fibrosis in renal tissues. Treatment of BXYS was correlated with a restoration of heart function and improvement of renal hemodynamics, lower serum and urine sCTGF, lower CTGF mRNA, CTGF, α-SMA and LRP expression in renal tissues and lower ECM deposition. In addition, experiments showed that treatment with BXYS reduced the α-SMA and LRP concentration in NRK-52E cells, which were similar experiments. In conclusion, the current study provided evidences that BXYS played a role in improving heart function and delaying the progress of renal fibrosis. Meanwhile, the CTGF-LRP pathway might be one of the therapeutic targets for myocardial infarction caused type 2 CRS which showed a positive change after BXYS treatment and is worthy of further exploration.
本研究旨在探讨中药补心益肾汤（BXYS）对心肌梗死所致2型心肾综合征（CRS）的治疗作用，并探索BXYS发挥作用的可能机制。采用左冠状动脉前降支结扎诱导的慢性心力衰竭（CHF）大鼠模型，分为假手术组、CHF模型组、福辛普利组、BXYS（0.4 g/kg）组和BXYS（0.8 g/kg）组。给药28天和60天后，评估心功能、肾血流动力学、神经内分泌因子、血清及尿液中可溶性结缔组织生长因子（sCTGF）浓度、肾组织中CTGF mRNA、CTGF、α-平滑肌肌动蛋白（α-SMA）和低密度脂蛋白受体相关蛋白（LRP）的表达。同时对肾组织进行组织学分析。通过检测NRK-52E细胞中CTGF、α-SMA等因子，设计实验验证上述实验结果。CHF大鼠表现出明显的病理生理变化，包括：肾血流动力学参数改变；心功能失调；血清血管紧张素II（AngII）、环磷酸鸟苷（cGMP）、血清肌酐（Scr）、血尿素氮（BUN）、C反应蛋白（CRP）、脑钠肽（BNP）浓度变化；血清和尿液sCTGF浓度升高；肾组织中CTGF mRNA、CTGF、α-SMA和LRP表达升高；肾组织细胞外基质（ECM）沉积增加和纤维化。BXYS治疗与心功能恢复、肾血流动力学改善、血清和尿液sCTGF降低、肾组织中CTGF mRNA、CTGF、α-SMA和LRP表达降低以及ECM沉积减少相关。此外，实验表明BXYS治疗可降低NRK-52E细胞中α-SMA和LRP浓度，与上述实验结果相似。总之，本研究提供证据表明BXYS在改善心功能和延缓肾纤维化进展中发挥作用。同时CTGF-LRP通路可能是心肌梗死所致2型CRS的治疗靶点之一，BXYS治疗后呈现阳性变化，值得进一步探索。
