Chen Wenzhong, Fan Zhiwen, Huang Canhui, Liu Junying
Department of Cardiovascular Medicine, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, China.
Department of Cardiology, The PLA 74th Group Army Hospital, Guangzhou, Guangdong 510300, China.
Evid Based Complement Alternat Med. 2022 Jun 15;2022:8644353. doi: 10.1155/2022/8644353. eCollection 2022.
To explore the potential and mechanism of action of poricoic acid A (PAA) in treatment of cardiorenal injury and fibrosis due to cardiorenal syndrome (CRS).
A CRS rat model was established by transabdominal subtotal nephrectomy (STNx). The experimental group was treated by gavage of PAA (10 mg/kg/day). After 8 weeks of treatment, echocardiography was utilized for detecting heart-related indexes in rats. HE and Masson staining were conducted to detect the degree of pathological damage and fibrosis in rat kidney tissue, respectively. In addition, serum blood urea nitrogen (BUN), serum creatinine (SCr), and 24-hour urine protein were measured biochemically. Also, the levels of inflammatory factors (IL-1, IL-6, and IL-10) in rat kidneys were measured using ELISA. Western blot was used to examine the expression of NF-B/MAPK pathway-related proteins.
In this study, a CRS rat model was successfully established by STNx surgery. PAA treatment could significantly alleviate the damage of heart and kidney function in CRS rats and reduce the pathological damage of kidney tissue and renal fibrosis. Meanwhile, PAA could also inhibit the renal inflammatory response through downregulating IL-1 and IL-6 levels in the kidney tissue and upregulating IL-10 level. Further mechanism exploration showed that the NF-B/MAPK signaling pathway was significantly activated in CRS rats, while PAA treatment could markedly inhibit the NF-B/MAPK signaling pathway activity in CRS rats.
PAA can obviously improve the pathological damage and fibrosis of renal tissue in CRS rats and maintain the function of the heart and kidney. The above functions of PAA may be achieved by inhibiting the NF-B/MAPK signaling pathway activity. Briefly speaking, PAA can serve as a potential drug for CRS treatment.
探讨茯苓酸A（PAA）治疗心肾综合征（CRS）所致心肾损伤及纤维化的潜力和作用机制。
通过经腹次全肾切除术（STNx）建立CRS大鼠模型。实验组通过灌胃给予PAA（10mg/kg/天）。治疗8周后，利用超声心动图检测大鼠心脏相关指标。分别进行HE和Masson染色以检测大鼠肾组织的病理损伤程度和纤维化程度。此外，生化检测血清尿素氮（BUN）、血清肌酐（SCr）和24小时尿蛋白。同时，采用ELISA法检测大鼠肾脏中炎症因子（IL-1、IL-6和IL-10）的水平。采用蛋白质免疫印迹法检测NF-κB/MAPK通路相关蛋白的表达。
本研究通过STNx手术成功建立了CRS大鼠模型。PAA治疗可显著减轻CRS大鼠的心肾功能损伤，减少肾组织的病理损伤和肾纤维化。同时，PAA还可通过下调肾组织中IL-1和IL-6水平、上调IL-10水平来抑制肾脏炎症反应。进一步机制探索表明，CRS大鼠中NF-κB/MAPK信号通路明显激活，而PAA治疗可显著抑制CRS大鼠中NF-κB/MAPK信号通路活性。
PAA可明显改善CRS大鼠肾组织的病理损伤和纤维化，维持心肾功能。PAA的上述作用可能是通过抑制NF-κB/MAPK信号通路活性实现的。简而言之，PAA可作为一种潜在的CRS治疗药物。
