Yin And Yang Huo Xue Tang Of Left Ventricular Hypertrophy In Renal Hypertensive Rats And Its Mechanism

Purpose:Hypertension is a kind of common cardiovascular disease, there are one-third patients accompanying with Left ventricular hypertrophy (LVH). LVH is closely related with over-burden of blood stream dynamics and neuroendocrine system, and it has been confirmed that rennin-angiotensin system (RAS) plays an important role in the occurrence and development of left ventricular hypertrophy. AngⅡis an essential active material which induces myocardial hypertrophy. Therefore, the medicine that can interdict RAS and AngⅡactivity can decrease the incidence rate of myocardial hypertrophy and it has benefit in reversing LVH. This research, using the classic LVH model (2 kidneys 1 clip, 2K1C) of G-RHR with kidney substance hypertension, the model is named as RH model, is to discuss the mechanism of Zi Yin Qian Yang Huo Xue decoction (ZQT) lowering the blood pressure and reversing the hypertension LVH, through studying ZQT influencing on blood pressure, mean carotid avterial pressure (mCAP), left ventricular end diastolic pressure (LVEDP), LV±dp/dt^max , left ventricular mass/body weight ratio (LVM/BW=LVMI) and angiotentionⅡin the blood and myocardial tissue of the 2K1C rats.Materials and Methods:1. Experimental medicine and reagent⑴Zi Yin Qian Yang Huo Xue decoction(ZQT) is composed of dried rehmannia root, CoacoasiaI Giehnia Root, Angelica sinensis, Radix Ophiopogonis, Spica prunellae, Barbary Wolfberry Fruit, Semen cassiae torae, Herba leonuri, Herba siegesbeckiae, Dragonbones.All above medicines were supplied by the 1st Hospital of Liaoning University of Traditional Chinese Medicine, and raw-material medicine mixed according to recipe portion after a second time dry, dipped in pure water as 6 times than the medical mixer for 2 hours at air temperature, and then decocted in slow fire for 3 times, each time cooking at least 1 hour, mixed all filtrate and concentrated to liquid containing raw medicine 4g per milliliter, reserved at -4℃in refrigerator.⑵Iodine AngiogenesisⅡRadioimmunoassay Kit was from Beijing Furui Biotechnology Company2. Experimental Animals The animals used in this experiment are the Sprague-Dawley rats, weight of the rats was from 180g to 220g, age was about 12 weeks old, and all of the rats were provided by the animal experimental center of China Medical University.3. GroupsExperimental rats were dividend into 3 groups, each group was 10 rats. The group was named as Sham-operation group(C), Model group (M) and Chinese medicine group (P).4. MethodsThe sham-operation group and model group were supplied with 0.9% Nacl to inject in the abdomen 80mg.kg^-1.d^-1 for 8 weeks. The Chinese medicine group was supplied with ZQT 30g.kg^-1.d^-1 gavages for 8 weeks.5. Study Contents⑴The foundation and evaluation of RH models⑵The influence of ZQT made to the blood pressure, mCAP, LVEDP, LV±dp/dtmax and LVMI of RH rats⑶The influence of ZQT made to AngⅡin the blood and myocardial tissue of RH rats⑷The observation on change of myocardial tissue of RH rats by transmission electron microscope(TEM)Results:1. The foundation and evaluation of RH models Compared with sham-operation group, the operation groups after the left renal artery partly stenos is, the systolic blood pressure(SBP) of 2K1C RH rats increased from before operation 100.6±4.38 mmHg to 160.37±4.82 mmHg, which had the significant difference (P<0.01).2. The influence of ZQT made to the blood pressure, mCAP, LVEDP, LV±dp/dt^max and LVMI of RH ratsComparing with the rats in group C, the mCAP, LVEDP and LVMI of the rats in group M, increased by 59.78 %( P<0.01), 204.94 %( P<0.01), and 26.85 %( P<0.01) respectively, was obviously higher than the rats in group C, but the LV+dp/dt^max of the rats in group M was decreased by 38.51 %( P<0.05), there was no significant to the group C and group M in LV-dp/dt^max. According to the above data, it showed the left ventricular hypertrophy was founded, the ventricular remodeling was occurred, and the myocardial function was decreased. Comparing with the rats in group M, the LV+dp/dt^max and LV-dp/dt^max of the rats in group P, was increased by 144.89% (P<0.01) and 101.90%(P<0.05), but the mCAP, LVEDP and LVMI of the rats in group P was decreased by 25.94%(P<0.01), 52.65%(P<0.05), and 18.40%(P<0.05) respectively. According to the above data, it showed the blood pressure was decreased significantly, the myocardial function was recovered, and the left ventricular hypertrophy was reversed. Based on these data, it means that, after taking ZQT, the rats in group P can decrease the blood pressure, promote the myocardial function and reverse the left ventricular hypertrophy.3. The change of expression of angiotentionⅡin the plasma and myocardial tissue Compared with the rats in group C, the concentration of AngⅡin the plasma and myocardial tissue of rats in group M was increased obviously, which had the significant difference (P<0.01). Compared with the rats in group M, the concentration of AngⅡin the plasma and myocardial tissue of rats in group P was decreased obviously, which had the significant difference (P<0.01 and P<0.05). Based on the data above, it shows that, after taking ZQT, the rats in group P can decrese the expression of AngⅡin the plasma and myocardial tissue.4. The observation on electron micrographs of myocardial cell of RH rats by transmission electron microscope (TEM) Myocardial cell ultra structure of rats was significantly different. C group, under the electron microscope, clear myocardial cells with normal stripes, muscle cell nucleus is located below the myofibril, myofibril traveling neatly, there is complete intercalated disk among the adjacent muscle fibers, intercalated discs at both ends of cells; M group, under the electron microscope, the filaments of ventricular Muscles become loose. Myofibril was arranged irregularly, it showed breakage and loss, widened intercalated disc, the basement membrane under the mild edema, nuclear hypnosis phenomenon is easy to see; P groups, under the electron microscope, myofibrils of myocardial cells was close to normal, is arranged closely, the shape of the muscle cell nuclei was close to the normal muscle cell nuclei, there was no fiber disorders, broken and missing, and close to the C group.ConclusionsZQT can improve the treatment of hypertension and left ventricular hypertrophy in RH rats. The mechanism of anti-hypertension and reversing LVH is possibly through decreasing AngⅡlevel in plasma and myocardial tissue of the RH rats, so the mechanism of ZQT to treat the hypertension and LVH is closely related to the rennin-angiotensin system(RAS).