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Study on Effects of Qishen Yiqi Drop Pills on the Left Ventricle Hypertrophy in Rats with Renavascular Hypertension

Author: ShuChangCheng
Tutor: WeiWanLin
School: Third Military Medical University
Course: Internal Medicine
Keywords: Qishen Yiqi drop pills valsartan Renovascular Hypertension left ventricular hypertrophy Extracellular signal-regulated kinase1/2 Connective tissue growth factor
CLC: R285.5
Type: Master's thesis
Year: 2011
Downloads: 63
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Abstract

Objective To explore the effects and mechanisms of Qishen yiqi drop pills on the left ventricle hypertrophy in rats with renovascular hypertension.Methods Fifty male Wistar rats,weighing about 200g each, were randomly divided into five groups（n=10）:negative control group （Sham）,operation group（2K1C）, Qishen yiqi drop pills large-dose group（2K1C+QSYQ250mg）, Qishen yiqi drop pills small-dose group（2K1C+QSYQ125mg）,and Valsartan group（2K1C+ Valsartan 30mg）. Four weeks after surgery operation,tap water was administered to rats in different groups by gavage. Qishen yiqi drop pills 250mg、125mg.kg^-1.d^-1 were administered to the Qishen yiqi drop pills large-and-small-dose groups,Valsartan 30mg/（kg.d） was administered to the Valsartan group and the same doses of saline were administered to the Sham operation group and 2K1C group for 8 weeks until the end of the experiment. After 8 weeks treatment,systolic blood pressure（SBP） and LVMI and LVWT were measured;pathologic changes of left ventricular myocardium were viewed with HE staining methed; CVF were detected by Van Gieson,and SOD、GSH-PX、ROS were detected by ELISA,and the expression of p-ERK1/2 and CTGF were detected by immunohistochemistry and Western blot.Results （1） 4 weeks after surgery operation,blood pressure in each of 2K1C group were more than 150mmhg, compared with sham-opration group,blood pressure in each of 2K1C group were significantly higher（P<0.01）, each of 2K1C group were no difference（P>0.05）. the model of renavascular hypertension in rats was stable and successful.（2） Pathologic changes of left ventricular myocardium with HE staining: 12 weeks after surgery operation, Under light microscope, HE staining of left ventricular muscle in the sham group, Cardiac muscle fiber lined up in order,the size and form of cardiac muscle cell were normal. HE staining of left ventricular muscle in the 2K1C group, Cardiac muscle fiber arrayed disorderly ,cells’diameters were increased .Qishen yiqi drop pills large-and-small-dose group and Valsartan group were mainly same to that of sham group,too.（3）Compared LVMI、LVWT、CVF in five groups:LVMI（mg/g） in sham operation group、2k1c group、Qishen yiqi drop pills large-and-small-dose group and Valsartan group were 1.74±0.17、2.28±0.28、1.98±0.16、2.09±0.14、1.97±0.17; LVWT（mm） in sham operation group、2k1c group、Qishen yiqi drop pills large-and-small-dose group and Valsartan group were 2.24±0.22、3.07±0.22、2.76±0.21、2.89±0.17、2.69±0.14;CVF（%） in sham group、2k1c group、Qishen yiqi drop pills large-and-small-dose group and Valsartan group were 0.45±0.13、4.73±1.04、0.94±0.22、2.53±0.61、0.81±0.20. The results showed that the LVMI、LVWT、CVF in 2K1C group were significantly increased （P<0.01）, when compared to the SHAM operation group.However, when compared to the 2k1c group, the LVMI、LVWT、CVF were significantly decreased in the Qishen Yiqi drop pills large-and-small-dose group and Valsartan group that the difference was not obviously among treatment groups（P>0.05）.（4）Compared SOD、GSH-PX、ROS in five groups:SOD（u） in sham operation group、2k1c group、Qishen yiqi drop pills large-and-small-dose group and Valsartan group were 105.12±7.20、97.58±6.26、111.63±5.97、103.41±5.19、113.56±6.22;GSH-PX（u） in sham operation group、2k1c group、Qishen yiqi drop pills large-and-small-dose group and Valsartan group were 86.51±4.24、80.58±6.95、91.69±7.52、87.14±5.71、94.50±8.55;ROS（umol） in sham operation group、2k1c group、Qishen yiqi drop pills large-and-small-dose group and Valsartan group were 10.20±1.38、12.31±2.31、9.81±1.41、10.71±1.45、9.29±1.32. The results showed that the SOD、GSH-PX were significantly decreased but ROS was significantly increased （P<0.05） in 2K1C group, when compared to the SHAM operation group.The results in Qishen Yiqi drop pills large-and-small-dose groups were not obviously significantly different（P>0.05）; when compared to the 2k1c group, the SOD、GSH-PX were significantly increased but ROS was significantly decreased（P<0.05）; when compared to the Valsartan group, the SOD、GSH-PX、ROS were not obviously difference（P>0.05）.（5） Immunocytochemical staining and semiquantitative analysis of P-ERK1/2 and CTGF in left ventricle: sham operated group:there are small amounts of fine particle in cadiocyte endochylema, diffused distribution,staining thinness,but it can not be seen in cellular nucleus and endangium. 2K1C group:expression of P-ERK1/2 and CTGF were obviously enhance in cadiocyte endochylema,amount of Buffy fine particle can be seen,distributed wide spreadly in cadiocyte endochylema,distributed like trabs staining deeply. Qishen Yiqi drop pills large-and-small-dose groups and valsartan group compared with 2K1C group, expression of P-ERK1/2 and CTGF were obviously decreased, amounts of fine particle in cadiocyte endochylema, diffused distribution. semiquantitative analysis of P-ERK1/2 in left ventricle were: 0.1670±0.0408、0.7367±0.1953、0.2378±0.0484、0.2810±0.0520、0.2350±0.0455.semiquantitative analysis of CTGF in left ventricle were: 0.1700±0.0508、0.8167±0.2557、0.2444±0.0802、0.3100±0.0789、0.2410±0.0595. The results showed that the P-ERK1/2 and CTGF in 2K1C group were significantly increased （P<0.01）, when compared to the SHAM operation group.The results in Qishen Yiqi drop pills large-and-small-dose groups were not obviously significantly different（P>0.05）; when compared to the 2K1C group, the protein expression of P-ERK1/2 and CTGF was significantly decreased（P<0.05）; when compared to the Valsartan group, the protein expression of P-ERK1/2 and CTGF were not obviously difference（P>0.05）.（6） Changes of p-ERK1/2 and CTGF expression in left ventricle of five groups by western blot:through grayscale analysis of P-ERK1/2 in sham operation group、2K1C group、Qishen yiqi drop pills large-and-small-dose group and Valsartan group were 65.91%、114.92%、78.45%、82.26%、64.05%. CTGF were 26.87%、119.16%、72.50%、87.63%、52.59%.When compared with 2K1C group, the sham operation group、Qishen yiqi drop pills large-and-small-dose group and Valsartan group,the protein expression of P-ERK1/2 were significantly decreased,were 49.01%、36.47%、32.66% and 50.86%.The protein expression of CTGF were significantly decreased,were 92.29%、46.66%、31.53% and 66.57%.Conclusions （1） In this study,the model of ventricular hypertrophy in rats with renavascular hypertension using 2k1c opration was stable and successful.（2）LVH in renavascular hypertension might be caused by increased expression of ROS,P-ERK1/2,CTGF protein and decreased expression of SOD、GSH-PX protein.（3） Qishen yiqi drop pills can limit the development of left ventricular hypertrophy induced by renal hypertension in rats. The same effect to Valsartan.（4） Qishen yiqi drop pills can limit the development of left ventricular hypertrophy caused by RHR,which might through the decreased expression of ROS and CTGF protein and inhibition signal transdution of ERK1/2.

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