参竹心康汤对慢性心衰大鼠心肌纤维化及TGF-β_1、CTGF表达的影响

Effect of Shenzhu Xinkang Decoction on Myocardial Fibrosis and Expressions of TGF-β_1 and CTGF in Rat with Chronic Heart Failure

目的:观察参竹心康汤对慢性心力衰竭大鼠心肌纤维化以及心肌TGF-β1、CTGF表达的影响,探讨该方抑制心肌纤维化,改善心室重构的可能作用机制。方法:SD大鼠72只随机分为6组:假手术组,模型组,卡托普利组,参竹心康汤低、中、高剂量组,每组12只。采用腹主动脉缩窄法制作心衰大鼠模型。于造模成功后,假手术组、模型组以蒸馏水10 m L/kg灌胃;卡托普利组以卡托普利混悬液7.8 mg/kg灌胃,低剂量组、中剂量组、高剂量组分别以中药煎液(含生药4.5 g/m L)11、22、44 g/kg灌胃,均为每日1次,连续给药8周。放射免疫法检测大鼠血浆血管紧张素Ⅱ(AngⅡ)水平、碱水解法检测心肌组织羟脯氨酸(HYP)含量,以Masson染色后图像分析测量心肌胶原容积分数(CVF)、心肌血管周围胶原面积和管腔面积比例(PVCA),免疫组化法检测心肌TGF-β1、CTGF的表达。结果:模型组AngⅡ与HYP水平、CVF与PVCA、TGF-β1与CTGF蛋白光密度值明显高于假手术组;卡托普利组、中剂量组、高剂量组上述指标均明显低于模型组与低剂量组;而低剂量组上述指标亦低于模型组。结论:TGF-β1、CTGF参与心衰大鼠心肌纤维化的发病;参竹心康汤可抑制慢性心衰大鼠心肌纤维化、改善心室重构,与该方降低心肌TGF-β1及CTGF表达有关。

Objective： To observe the effect of Shenzhu Xinkang Decoction on the myocardial fibrosis in chronic heart failure rats and the myocardial cell＇s expressions of TGF-β1 and CTGF and explore the mechanism of how the decoction could inhibit the myocardial fibrosis and improve the ventricular remodeling. Methods： Seventy-two rats with chronic heart failure were enrolled and randomly divided into six groups： Control group（n = 12）,Model group（n = 12）,Captopril group（n = 12） and Shenzhu Xinkang Decoction groups with low（n = 12）,medium（n = 12） and high doses（n = 12）.Each group＇s 12 heart failure rat model was set up through the abdominal aortic banding method. The control and model groups＇ rats were given by gavage with distilled water of 10 m L; Captopril group with Captopril mixed suspension of 7. 8mg; the low,medium and high dose groups with TCM decoction（including crude drugs of 4. 5 g/m L） of 11 g,22 g,44 g.All groups were given by gavage once a day for 8 weeks. And then test the Ang II in plasma with the RIA method; the HYP in myocardial tissue with the alkaline hydrolysis method; the TGF-β1 and CTGF in myocardial cell with the IHC method and measure the CVF and PVCA in the Masson staining image. Results： The model group showed a higher level of protein optical density value in Ang Ⅱ,HYP,CVF,PVCA,TGF-β1 and CTGF than the control group while the Captopril group,medium dose group,high dose group showed a much lower level in these indexes and the low dose group also got lower indexes than the model group. Conclusion： The TGF-β1 and CTGF are involved in the trigger of the rat myocardial fibrosis. Shenzhu Xinkang Decoction could inhibit the CHF rat＇s myocardial fibrosis and improve the ventricular remodeling through reducing the myocardial cell＇s expressions of TGF-β1 and CTGF.