中药降压脉净对心肌组织转化生长因子-β_1的影响及干预心肌纤维化的作用

Effect of TCM formula(Jiangya Maijing granules,JMG)on myocardial TGF-β_1 and intervention of myocardial fibrosis in SHR

目的探讨中西医结合方法预防和干预自发性高血压大鼠心室重构心肌纤维化的病理改变及其作用机制。方法自发高血压大鼠(SHR)8周龄40只,随机分为4组,每组10只,并以SD大鼠8周龄10只作为对照组,分别进行药物观察,疗程20周。观察:心脏重量指数,心肌胶原容积分数(CVF),血管周围胶原面积(PVCA),Ⅰ、Ⅲ型胶原的表达。免疫组织化学法检测心肌组织转化生长因子-β(1TGF-β1)蛋白水平和RT-PCR检测心肌组织内TGF-β1mRNA的表达。结果①心脏重量指数、CVF、PVCA:治疗组与模型组比较有显著性减少,与西药对照组和中药对照组比较亦有减少。②病理学改变:偏光镜下观察Ⅰ、Ⅲ型胶原的表达中治疗组的表达明显比模型组减少,与西药对照组和中药对照组比较也有减少趋势。③TGF-β1:治疗组的药后值显著地低于模型组(P<0.01),同时也显著低于西药组(P<0.05)。结论①心肌中胶原蛋白含量明显增加的机制可能与转化生长因子-β1的高表达有关。②中药降压脉净剂具有抑制自发性高血压大鼠心肌纤维化的作用。其作用机制可能与抑制TGF-β1的高表达有关,在干预和逆转心肌纤维化方面优于单纯西药络活喜对照组,也有优于中药对照组的趋势。

Objective To prevent and reverse ventricle remodeling- fibrosis by the combination of TCM with Western medicine, and to explore mechanism by detecting some related factors. Methods 8-week-old SHR rat was randomly divided into 4 groups： model control group （SHR rat treated with distilled water）, treatment group （treated with JMG plus Nifedipine i.g）,Western medicine control group （treated with Nifedipine i.g only）, other formula of Chinese medicine control group （treated with Niuhang-Jiangya pills plus Nifedipine i.g）, each group consisted of 10 rats, Normal control group with 10 normal SD rats （treated with distilled water）.The course of treatment was 20 weeks. After 20-week treatment, rats was sacrificed, examination with heart weight index （HWI）, myocardium collagen volume fraction （CVF） and perivascular collagen area （PVCA） were measured. The change of collagen in myocardium pathological section and the expression of collagen I and III were observed. The expressions of transforming growth factor-β1 protein level and mRNA level in SHR myocardium were examined with immunohistochemical and RT-PCR method. Results （1）HWI,CVF,PVCA： Compared with model group, those of treatment group were significantly decreased（P〈0.01 ）, and its effect was superior to Western medicine control group and Chinese medicine control group. （2）Pathology change： The expressions of collagen Ⅰ and Ⅲ of treatment group were also lower than those in model group, Western medicine control group and Chinese medicine control group. （3）TGF-β1：There was no statistic difference between treatment group and SD group. Compared with model and Western medicine control group, the TGF-β1 levels of treatment group were obviously decreased. Conclusion （1）28-week-old SHR rats, compared with SD rats, the heart weight index and collagen fibers were significantly increased, the content of collagen protein （type Ⅰ andⅢ ） was also increased in myocardium. The mechanism might be related to high expression of TGF-β1. （2）JYMG could inhibited myocardial fibrosis, which was caused by hypertension. The possible mechanisms were related to promote the degradation of myocardium interstitial collagen, and inhibit high expressions of TGF-β1. Intervention and reversal of myocardial fibrosis in JYMJ group was better than that in control group of Western medicine, it was apt to be superior to control group of Chinese medicine.