基于"心应夏"理论探讨TRP热敏通道对慢性心衰大鼠心功能与结构的调控作用OA
Regulatory Effect of TRP Thermosensitive Channels on Cardiac Function and Structure in Chronic Heart Failure Rats Based on the"Heart Corresponding to Summer"Theory
[目的]观察夏冬季节温度变化对慢性心力衰竭(chronic heart failure,CHF)大鼠心功能与结构的影响,并从温度敏感的瞬时受体电位(transient receptor potential,TRP)-Ca2+-Ras同源基因家族蛋白A-Rho相关卷曲螺旋蛋白激酶(Ras homolog family member A-Rho-associated coiled-coil containing protein kinase,RhoA-ROCK)信号通路的角度,探讨"心应夏"的生物学机制.[方法]以SD大鼠为研究对象,使用智能气候箱分别模拟夏冬季节温度,每季大鼠均随机分为生理组、CHF组、伪手术组.饲养8周后取心肌组织,采用超声心动描记术检测心功能与结构变化;HE染色观察心肌病理改变,Masson染色评估心肌纤维化程度.采用ELISA检测TRP热敏通道指标心肌瞬时受体电位香草酸 4(transient receptor potential vanilloid 4,TRPV4)、瞬时受体电位锚定蛋白 1(transient receptor potential ankyrin 1,TRPA1)、RhoA、ROCK1、肌球蛋白轻链(myosin light chain,MLC)、转化生长因子-β1(transforming growth factor-β1,TGF-β1)水平;邻甲酚酞络合酮(o-cresolphthalein complexone,OCPC)法检测心肌Ca2+浓度.[结果]CHF组大鼠心功能与结构改变呈现出夏季优于冬季的季节趋势.与生理组与伪手术组比较,CHF组心肌TRPV4、TRPA1水平均上调,TRPV4水平在夏季组上调显著(P<0.01),TRPA1水平在冬季组上调显著(P<0.05).CHF组心肌Ca2+、RhoA、ROCK1、MLC、TGF-β1的季节性节律与心功能、结构变化相反,呈现夏低冬高的季节性趋势.[结论]"心应夏"的生物学机制可能是季节温度变化激活了心肌组织温度敏感的TRPV4、TRPA1通道,启动Ca2+信号及其下游RhoA-ROCK信号通路,引发一系列与夏季相应的生理及病理效应.
[Objective]To investigate the effects of temperature changes in summer and winter on cardiac function and structure in rats with chronic heart failure(CHF),and to explore the biological mechanisms underlying the"heart corresponding to summer"phenomenon from the perspective of the thermosensitive transient receptor potential(TRP)-Ca2+-Ras homolog family member A-Rho-associated coiled-coil containing protein kinase(RhoA-ROCK)signaling pathway.[Methods]Taking SD rats as the research subjects,climate-controlled chambers were used to simulate summer and winter temperatures.In each season,the rats were randomly assigned to physiological,CHF,and sham-operated groups.After 8 weeks of feeding,myocardial tissue was retrieved.Cardiac function and structural changes were assessed by echocardiography;myocardial pathological changes were observed after HE staining,the degree of myocardial fibrosis was assessed with Masson's staining;ELISA was used to detect the levels of TRP thermosensitive channel indicators,including myocardial transient receptor potential vanilloid 4(TRPV4),transient receptor potential ankyrin 1(TRPA1),RhoA,ROCK1 and myosin light chain(MLC),and transforming growth factor-β1(TGF-β1);myocardial Ca2+concentration was measured by using the o-cresolphthalein complexone(OCPC)method.[Results]CHF group exhibited seasonal trends in cardiac function and structural alterations,with a seasonal trend where summer was superior to winter.Compared with physiological group and sham-operated group,both TRPV4 and TRPA1 levels in myocardial tissue were upregulated in CHF group;TRPV4 levels were significantly upregulated in summer groups(P<0.01),while TRPA1 levels were significantly upregulated in winter groups(P<0.05).In contrast to cardiac function and structural changes,seasonal rhythms of myocardial Ca2+,RhoA,ROCK1,MLC and TGF-β1 in CHF group exhibited a seasonal trend of lower levels in summer and higher levels in winter.[Conclusion]The biological mechanism of the"heart corresponding to summer"theory may be that seasonal temperature changes activate thermosensitive TRPV4 and TRPA1 channels in myocardial tissue,initiate Ca2+signaling and its downstream RhoA-ROCK signaling pathway,and trigger a series of physiological and pathological effects corresponding to summer.
张文静;黄雪杰;彭宜璐;康帅;申占国;刘晓燕
北京中医药大学中医学院 北京 100029北京中医药大学中医学院 北京 100029北京中医药大学中医学院 北京 100029北京中医药大学中医学院 北京 100029北京中医药大学中医学院 北京 100029北京中医药大学中医学院 北京 100029
医药卫生
心应夏夏冬季节温度慢性心力衰竭TRPV4TRPA1RhoA-ROCK信号通路
heart corresponding to summersummer and winter seasonstemperaturechronic heart failureTRPV4TRPA1RhoA-ROCK signaling pathway
《浙江中医药大学学报》 2026 (7)
811-820,10
国家自然科学基金项目(81973716)National Natural Science Foundation Project(81973716)
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