坎离颗粒对心衰大鼠膈肌张力及细胞肌浆网钙转运的影响

Effects of “Kanli Granule”on Diaphragm Tension and Calcium Transport of Sarcoplasmic Reticulum in Rats with Chronic Heart Failure

目的:探讨中药坎离颗粒对腹主动脉缩窄致慢性心衰大鼠膈肌细胞肌浆网钙转运及膈肌张力的影响。方法:采用腹主动脉缩窄法制备Wistar大鼠左室舒张功能不全模型。分为假手术组、模型组、坎离颗粒组、培哚普利组。坎离颗粒组、培哚普利组分别于造模后1周予坎离颗粒和培哚普利,其余两组予双蒸水,共干预32周。干预结束后处死各组大鼠并取膈肌,离体状态下测定大鼠膈肌抗疲劳能力及张力恢复程度,Fura-2法检测各组大鼠膈肌细胞肌浆网钙摄取和释放功能,定磷法测定肌浆网钙泵(SERCA2a)的活性。结果:1腹主动脉缩窄32周心衰大鼠的膈肌抗疲劳能力下降、张力恢复程度降低;2受损膈肌细胞肌浆网(SR)Ca2+-ATP酶活性下降,钙摄取速率降低,钙释放速率有下降趋势;3以中药验方坎离颗粒干预,可显著增加膈肌抗疲劳能力和张力恢复程度,提高膈肌细胞SR的Ca2+-ATP酶活性,增加SR钙摄取速率。结论:腹主动脉缩窄所致舒张性心衰大鼠存在骨骼肌张力减退,可能与肌细胞SR的Ca2+-ATP酶活性减弱所致SR钙转运障碍有关;坎离颗粒干预可逆转这种病理改变。

Objective： To investigate the effects of ＂Kanli Granule＂ on diaphragm tension and calcium transport of sarcoplasmic reticulum （SR） in rats with chronic heart failure （CHF） . Methods： Prepared the diastolic heart failure Wistar rat models with abdominal aortic coarctation. Divided the rats into sham operation group, model group, ＂Kanli Granule＂ group and perindopril group. One week after modeling, the rats in the ＂Kanli Granule＂ group and perindopril group were intervened separately by ＂ Kanli Granule＂ and perindopril for 32 weeks. The rats were executed at the end of 32nd week and the diaphragms were sampled. The fatigue resistance and the tension recovery degree of the rat diaphragm in vitro, and the muscle SR calcium uptake and release function was detected by fura-2 method, and the SR calcium pump （SERCA2a） activity by phosphorus measurement. Results： ① The fatigue resistance of the diaphragm decreased in the CHF rats due to abdominal aortic coarctation for 32 weeks, and its tension recovery degree reduced as well; ② SR Ca2 ＋ -ATP activity of the damaged diaphragm decreased, and its calcium uptake reduced too, with the declined intendance of calcium release; ③ Intervention with ＂Kanli Granule＂ may significantly increase the capacity of diaphragmatic fatigue resistance and tension recovery of the CHF rat, and increase the diaphragm SR Ca2 ＋ -ATP activity and SR calcium uptake rate. Conclusion ： There was skeletal muscle hypotonia in the diastolic heart failure rat induced by abdominal aortic coarctation, which may be associated with SR calcium transport disorders in the muscle cells due to SR Ca2＋ -ATP activity decreased. This pathology change may reversed by the intervention with ＂Kanli Granule＂.