胆固醇酯转运蛋白在家兔心脏肥大中表达的实验研究

李洪铭; 李磊; 孟红旭; 邱雨美; 谢梦蝶; 马彦雷; 史跃; 汤喜兰

doi:10.12125/j.chj.202106069

胆固醇酯转运蛋白在家兔心脏肥大中表达的实验研究

Experssion of cholesteryl ester transfer protein in rabbits with cardiac hypertrophy

摘要

摘要:
目的复制异丙肾上腺素致家兔心脏肥大模型，考察胆固醇酯转运蛋白（CETP）的表达变化。
方法将雄性新西兰兔随机分为正常组和模型组。模型组采用腹腔注射异丙肾上腺素15 mg/(kg·d)（分早晚2次进行）建立家兔心脏肥大模型，正常组腹腔注射等体积的生理盐水，连续14 d后，取血、心脏和肺脏，分离左、右心室，考察脏器指数；HE染色观察心肌组织形态学改变；RT-PCR法检测心脏肥大相关胚胎基因ANP、β-MHC mRNA表达；检测血清TG、TC、LDL-C及HDL-C的含量；检测左心室CETP的mRNA水平、蛋白表达及含量。
结果与正常组比较，模型组家兔心脏质量指数（HW/BW）和左心室质量指数（LVW/BW）显著增加（P<0.05），右心室质量指数（RVW/BW）和肺脏质量指数（LW/BW）有增加的趋势，左心室心肌细胞体积明显增大，间质增宽，左心室ANP、β-MHC的mRNA表达显著上调（P<0.05）。与正常组比较，模型组家兔血清TG含量显著升高（P<0.05），TC、LDL-C水平呈升高趋势，HDL-C水平呈下降趋势，模型组家兔左心室组织中CETP mRNA水平和蛋白表达均显著上调（P<0.05），CETP含量显著增加（P<0.05）。
结论在异丙肾上腺素诱导的家兔心脏肥大模型中，CETP表达上调，但其是否与心脏肥大有关还有待进一步深入研究。本研究结果为后续研究CETP与心脏肥大的关系提供了理想动物模型。

Abstract:
AIM To investigate the expression of cholesteryl ester transfer protein (CETP) in isoproterenol induced cardiac hypertrophy in rabbits.
METHODS Twelve male New Zealand rabbits were randomly divided into a model group (n=6) and a control group (n=6). Cardiac hypertrophy was induced in the model group by daily isoproterenol administration 15 mg/(kg·d) for 14 days, while the control group was treated similarly with saline. At the end of the experimental period, samples of serum, heart and lungs were collected. Cardiac hypertrophy was quantified by the ratios of heart weight to body weight (HW/BW), the ratios of left ventricle weight to body weight (LVW/BW), the ratios of right ventricle weight to body weight (RVW/BW) and the expressions of fetal genes including ANP and β-MHC. The ratio of lung weight to body weight (LW/BW) was also detected. The morphological changes in the left ventricle tissue were observed by HE staining and the contents of serum TG, TC, LDL-C and HDL-C were detected. CETP in left ventricle was further observed by fluorescence quantitative PCR, Western blot and enzyme linked immunosorbent assay, respectively.
RESULTS Isoproterenol 15 mg/(kg·d) treatment for 14 days induced cardiac hypertrophy as evidenced by the increases of HW/BW and LVW/BW, the enlargement of myocardial cells with widened interstitium, as well as the up-regulations of the hypertrophy-related fetal gene expressions (P<0.05). An increasing tendency of RVW/BW and LW/BW was observed in the model group in comparison with that in the control group. Compared with those in the control group, the content of serum TG was significantly increased (P<0.05) and the contents of serum TC and LDL-C showed an increasing tendency, whereas the content of serum HDL-C showed a decreasing trend. Further research found that isoproterenol significantly induced the up-regulations of CETP mRNA level and CETP protein expression as well as the increase of CETP content in left ventricle (P<0.05).
CONCLUSION CETP expression is up-regulated in isoproterenol induced cardiac hypertrophy in rabbits. But whether it is involved in cardiac hypertrophy remains to be futher studied. This study may provide an ideal animal model fo the follow-up study of the relationship between CETP and cardiac hypertrophy.

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