基于AVP-V2R-cAMP-AQP2 信号通路探讨强心康治疗慢性心力衰竭的作用机制
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R285.5

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福建省自然科学基金项目(2023J011856);漳州市自然科学基金项目(ZZ2024J21)


Exploration on the Mechanism of Qiangxinkang in the Treatment of Chronic Heart Failure Based on the AVP-V2R-cAMP-AQP2 Signaling Pathway
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    摘要:

    目的:探讨中药方剂强心康对慢性心力衰竭(CHF) 大鼠的治疗作用及其与精氨酸血管加压素(AVP) -V2受体(V2R) -环磷酸腺苷(cAMP) -水通道蛋白2(AQP2) 信号通路的关系。方法:在50只SPF级Wistar大鼠中随机选取10只为空白组,余下40只大鼠采用腹腔注射阿霉素法制备CHF模型,剔除未成模及死亡的大鼠后,将剩余的造模大鼠分为模型组、强心康高剂量组、强心康低剂量组,每组10只。空白组、模型组分别给予10 mL/kg蒸馏水灌胃,强心康高剂量组、强心康低剂量组分别按10 mL/kg体积予23.5 g/(kg·d)、5.89 g/(kg·d) 的强心康药液灌胃。记录各组大鼠的尿量、尿钠排泄率、体质量变化情况。超声心动图观察大鼠心功能指标左心室短轴缩短率(LVFS)、左心室射血分数(LVEF) 变化,蛋白质印迹法检测大鼠肾脏组织V2R、AQP2表达,酶联免疫吸附法检测大鼠血清及肾组织中AVP、cAMP表达。结果:与空白组比较,模型组大鼠体质量基本不增加甚至下降(P<0.05), 尿量、尿钠排泄率均降低(P<0.05), LVFS、LVEF 均下降(P<0.05), 肾脏组织V2R、AQP2 蛋白表达均升高(P<0.05), 血清及肾组织AVP、cAMP 水平均升高(P<0.05)。与模型组比较,强心康高剂量组、强心康低剂量组大鼠尿量增加(P<0.05),尿钠排泄率升高(P<0.05);强心康高剂量组超声心动图LVFS、LVEF水平升高(P<0.05);强心康高剂量组大鼠肾脏组织中V2R、AQP2蛋白的相对表达量降低(P<0.05);强心康低剂量组大鼠肾脏组织中AQP2蛋白的相对表达量降低(P<0.05),而V2R蛋白的相对表达量虽有降低趋势,但差异无统计学意义(P>0.05);强心康高剂量组大鼠血清及肾组织中AVP、cAMP的水平均降低(P<0.05);强心康低剂量组大鼠肾组织中AVP、cAMP水平降低(P<0.05),而血清中AVP、cAMP的水平虽有降低趋势,但差异无统计学意义(P>0.05)。结论:强心康可通过抑制AVP-V2R-cAMP-AQP2信号通路,调节水钠代谢,改善CHF大鼠心脏收缩功能。

    Abstract:

    Abstract: Objective: To investigate the therapeutic effect of Qiangxinkang, the traditional Chinese medicine prescription,on chronic heart failure (CHF) rats,and to explore its relationship with the arginine vasopressin (AVP)- V2 receptor (V2R)-cyclic adenosine monophosphate (cAMP)-aquaporin 2 (AQP2) signaling pathway. Methods: Among 50 SPF-grade Wistar rats, 10 were randomly selected as the blank group, and the remaining 40 rats were used to establish CHF models by intraperitoneal injection of Doxorubicin. After excluding rats that failed to model or died, the remaining model rats were divided into model group, Qiangxinkang high-dose group, and Qiangxinkang low-dose group, with 10 rats in each group. The blank group and model group were intragastrically administered 10 mL/kg distilled water, while the Qiangxinkang high-dose and low-dose groups were intragastrically administered Qiangxinkang solution at doses of 23.5 g(/ kg·d) and 5.89 g(/ kg·d),respectively,at a volume of 10 mL/kg. Changes in urine output,urinary sodium excretion rate,and body weight of each group were recorded. Echocardiography was used to observe changes in fractional shortening (LVFS) and ejection fraction (LVEF) of the left ventricular. Western blot was performed to detect the expression of V2R and AQP2 in rat renal tissues. Enzyme-linked immunosorbent assay (ELISA) was used to measure the expression of AVP and cAMP in serum and renal tissues. Results:Compared with the blank group,the model group showed no significant increase and even decreased in body weight (P<0.05), decreased urine output and urinary sodium excretion rate (P<0.05), decreased LVFS and LVEF of the left ventricular (P<0.05), increased expression of V2R and AQP2 proteins in renal tissues (P<0.05), and increased levels of AVP and cAMP in serum and renal tissues (P<0.05). Compared with the model group, the Qiangxinkang high-dose and low-dose groups showed increased urine output (P<0.05) and increased urinary sodium excretion rate (P<0.05). The Qiangxinkang high-dose group showed increased LVFS and LVEF of the left ventricular on echocardiography (P<0.05). The relative expression levels of V2R and AQP2 proteins in renal tissues were decreased in the Qiangxinkang high-dose group (P<0.05). The relative expression level of AQP2 protein in renal tissues was decreased in the Qiangxinkang low-dose group (P<0.05),while the relative expression level of V2R protein showed a decreasing trend but without statistical significance (P>0.05). The levels of AVP and cAMP in serum and renal tissues were decreased in the Qiangxinkang high-dose group (P<0.05). The levels of AVP and cAMP in renal tissues were decreased in the Qiangxinkang low-dose group (P<0.05), while the levels of AVP and cAMP in serum showed a decreasing trend but without statistical significance (P>0.05). Conclusion:Qiangxinkang can regulate water-sodium metabolism and improve cardiac systolic function in CHF rats by inhibiting the AVP-V2R-cAMP-AQP2 signaling pathway.

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苏宝连,陈晖,柯庚申.基于AVP-V2R-cAMP-AQP2 信号通路探讨强心康治疗慢性心力衰竭的作用机制[J].新中医,2026,58(15):186-194

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  • 在线发布日期: 2026-08-05
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