血压平逆转2K1C肾性高血压大鼠左室重构的作用及其机理的研究

Reverse effects and its mechanisms of Xueyaping on left ventricle remodeling resulting from renal hypertension induced by 2K1C in rats

目的:研究血压平逆转二肾一夹肾性高血压大鼠左室重构的作用及其机理。方法:建立2K1C肾性高血压大鼠(RHR)模型,术后8周40只RHR随机分为5组,每组8只,分为:血压平大、中、小剂量组(73、36.5、18.25g·kg-1·d-1);依那普利组(10g·kg-1·d-1);模型组,另取8只大鼠作为假手术对照组。模型组和假手术组灌服等容量水,疗程8周。手术前及术后每周测血压1次,给药第8周末,各组测量大鼠体重(BW),眼眶放血2ml,断头处死大鼠,迅速取出心脏,去除心房、右室游离壁,左室及室间隔称重(LVW),计算LVW/BW之比。采用放免法检测血清PCⅢ,心肌组织石蜡切片HE染色及SP免疫组化染色高清晰度图像分析系统测量心肌细胞形态参数及原癌基因cmyc和cfos表达阳性细胞的平均光密度值。结果:血压平降低血压,降低左室重量(LVW)、左室重量指数(LVW/BW)、心肌细胞体积及血清PCⅢ含量,抑制原癌基因cmyc和cfos的表达,血压平大、中剂量组LVW、LVW/BW及血清PCⅢ含量明显低于模型组(P<0.01),图像分析心肌细胞形态参数(面积、周长、平均直径、长径及短径)及cmyc、cfos表达阳性的心肌细胞平均光密度值明显低于模型组(P<0.01),与假手术组接近(P>0.05)。结论:复方中药血压平具有逆转2K1C肾性高血压大鼠左室重构的作用,其降低血压和血清PCⅢ含量、抑制Ⅲ型胶原合成、防治心肌纤维化及降低原癌基因cmyc和cfos的表达、抑制心肌细胞肥大、减轻左心室肥厚是其逆转二肾一夹肾性高血压大鼠左室重构的部分机制。

AIM： To investigate the reverse effects and its mechanisms of Xueyaping on left ventricle remodeling resulting from renal hypertension induced by 2K1C in rats （RHR）. METHODS： Renal hypertension rat was induced by 2K1C. 40 RHRs were randomly divided into 5 groups with 8 rots in each group 8 weeks after induction including： group 1 was the large dosage Xueyaping （73g·kg^-1·d^-1） group , group 2 was the medium dosage Xueyaping （36.5g·kg^-1·d^-1） group, group 3 was the low dosage Xueyaping （18.25g·kg^-1·d^-1） group, group 4 was the enalapril group （10 mg·kg^-1·d^-1）, and group 5 was the model group. Besides, psydeo-operation was performed on another 8 rats and set as the control group. Iso-volume pure water was poured into stomach in group 4 and group 5 for 8 weeks. Blood pressure was taken before operation and once a week after operation. By the end of the eighth week, the body weight was measured and 2 ml blood was taken through eye sockets. The rats were then put to death by cuttign off their heads. The heart was removed rapidly and atrium and free wall of right ventricle were abounded. The left ventricle and interventricular septal weight （LVW） were measured. LVW/BW ratios were calculated. Serum PCⅢ was measured using radio-immune method. Paraffin embedded heart tissue was cut and stained with HE and SP immunohistochemistry. Conformation parameters and mean light density of positive c-myc and c-fos expression heart muscle cells were measured using high resolution picture analyzing system. RESULTS： Xueyaping had the effects of lowering blood pressure, decreasing LVW, LVW/BW, heart muscle cell volume, serum PCⅢ, and the expression of c-myc and c-fos. SBP, LVW, LVW/BW and serum PCⅢ in group 1 and 2 were significantly lower than those in group 5 （P〈0.01）. Conformation parameters of heart muscle cells （area, circle length, mean diameter, length of long and short axes） and mean light density of positive c-myc and c-fos expression cell in group 1 and 2 were significantly lower than those in group 5 （P〈0.01）, and were close to those in the sham operation group （P〉0.05）. CONCLUSION： Xueyaping has the effects of reversing left ventricle remodeling in hypertensive rats induced by 2K1C. The effects may be related to the partial mechanisms of reversing left ventricle remodeling in hypertensive rats induced by 2K1C.