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目的:研究葛根素对异丙肾上腺素(isoprenaline,ISO)诱导的大鼠心肌纤维化和心肌结缔组织生长因子(connective tissue growth factor,CTGF)的影响。方法:雄性SD大鼠随机分成4组:①造模组(M组)16只,采用0.05%ISO(5mg·kg-1.d-1×10d)皮下注射制作大鼠心肌纤维化模型;②早期干预组(Pa组)12只,造模同时给予葛根素(100mg·kg-1.d-1)腹腔注射56d;③后期治疗组(Pp组)12只,造模10d后给予葛根素腹腔注射46d;④对照组(C组)8只。对各组计算左心室质量指数,检测左室心肌组织中羟脯氨酸浓度,进行VG染色、免疫组化染色,测算胶原容积积分(collagen volume fraction,CVF)和CTGF蛋白含量,RT-PCR检测CTGF mRNA水平。结果:Pa组、Pp组和M组的左心室质量指数、CVF、心肌组织羟脯氨酸浓度和CTGF均较C组明显增加(P<0.01);Pa组和Pp组的左心重量指数、CVF、心肌组织羟脯氨酸浓度和CTGF均较M组明显减少(P<0.01),Pa组减少更明显。结论:葛根素减少胶原沉积,从而减轻和延缓ISO诱导的心肌纤维化,早期干预效果更明显,这种作用机制可能是通过抑制CTGF的过度表达来实现。
Objective: To study the effects of puerarin on isoprenaline (ISO)-induced myocardial fibrosis and cardiac connective tissue growth factor (CTGF) in rats. METHODS: Male Sprague-Dawley rats were randomly divided into 4 groups: 1 Mock-up group (M group). Rats’ myocardial fibrosis model was established by subcutaneous injection of 0.05% ISO (5 mg·kg-1.d-1×10d); 2 In the early intervention group (Pa group), 12 rats were given intraperitoneal injection of puerarin (100 mg·kg-1.d-1) for 56 days; 3 rats in the late treatment group (Pp group) were given 10 days later, and puerarin was given intraperitoneally. Injection 46d; 4 control group (C) 8. Left ventricular mass index was calculated for each group. The concentration of hydroxyproline in left ventricular myocardium was measured. VG staining and immunohistochemical staining were performed. Collagen volume fraction (CVF) and CTGF protein content were measured. RT-PCR detection was performed. CTGF mRNA levels. RESULTS: Left ventricular mass index, CVF, hydroxyproline concentration and CTGF in the Pa group, Pp group, and M group were all significantly higher than those in the C group (P<0.01); left heart weight index in the Pa group and the Pp group. CVF, myocardial tissue hydroxyproline concentration and CTGF were significantly decreased compared with M group (P<0.01), and Pa group was more significantly reduced. CONCLUSION: Puerarin can reduce collagen deposition, thus reducing and delaying ISO-induced myocardial fibrosis. Early intervention is more effective. This mechanism may be achieved by inhibiting the over-expression of CTGF.