The Side Of Qianyangtongluo Prescription On Liver Yang Left Ventricular Hypertrophy In Spontaneously Hypertensive Rats And Its Mechanism

Objective: The disease of Left ventricular hypertrophy was due to pressure overload long-term, and some growth factors like catecholamines and angiotensinâ…¡to stimulate myocardial hypertrophy and interstitial fibrosis. It is a complication of hypertension, and is sudden death, coronary heart disease and congestive heart failure independent, major risk factors. There is no effective treatment to prevent the occurrence of left ventricular hypertrophy. Therefore, there are great significance in improving the prognosis of hypertension and the survival. This is rely on the advantages of Chinese medicine to find new ways to effectively slow down the treatment myocardial fibrosis and reverse left ventricular hypertrophy. This research is based on dialectical thinking, use an animal model of disease and syndrome, in spontaneously hypertensive rats fed Fuzitang to copy Aconite Decoction Act permits hyperactivity hypertension rat model of left ventricular hypertrophy. Then by animal experiments, to observe the side of Qianyangtongluo prescription on the blood and heart tissue catecholamine levels, the expression of angiotensinâ…¡receptors, ET receptor protein expression and other indicators and to explore the mechanism of its treatment. Futher reveal the liver yang nature of left ventricular hypertrophy, to procede experimental evidence for the treatment of the disease.Methods:32 spontaneous hypertensive rats(SHR), 14 weeks old, male, weight from 280g³20g, blood pressure between 160mmHg¹90mmHg, were randomly divided into the model group (which was abbreviated to"M group"), the low-dose Qianyangtongluo prescription group (which was abbreviated to"L group"), the high-dose Qianyangtongluo prescription group (which was abbreviated to"H group") and the captopril control group (which was abbreviated to"C group"). Meanwhile, 8 Wistar rats, male, being bought weight from 280g³20g, were regarded as the normal group (while was abbreviated to"N group"). After the rats were fed adaptively for a week, the experiment was done. In accordance with the records, 32 SHR were lavaged with Fuzi decoction (10ml·kg^-1·d^-1, which is equal with 2g·kg^-1·d^-1) at the same time everyday. The whole process was 4 weeks. In the process, we observed the change of basic situation: coat color, irritability level, water intake, rotation time and so. When prompted for the modeling is successful, stop the Fuzitang decoction irrigation, N group and M group were lavaged with the same dose distilled water, C group were lavaged with captopril solution (10ml·kg^-1·d^-1, which is equal with 8mg·kg^-1·d^-1), L group were lavaged withQianyangtongluo prescription (10ml·kg^-1·d^-1, which is equal with 24.6g·kg^-1·d^-1), H group were lavaged with Qianyangtongluo prescription (10ml·kg^-1·d^-1, which is equal with 49.2g·kg^-1·d^-1). All of the rats were fed with tap water and common animal feeds. The process was 6 weeks. Measuring all the rats'blood pressure, each rat was measured 3 times at the same time every Saturday, using the average as the actual blood pressure of that week. At the end of the experiment, rats were decapitated to collect blood, measuring the required indicators. Left ventricular mass with analytical balance weighing, morphology of myocardial cells by HE staining, measurement of caecholamine content of plasminogen immune, RT-PCR detected the expression of angiotensin receptor, immunohistochemistry and HE staining the protein expression of ET receptor, detected the ET, NO, Angâ…¡levels by radioimmunoassay.Results:1 General behavior observationThe period of building model, blank group rats'pelage is slippery and luster, spirit is in good condition, action is quick, temperament is docile; Hypertensive rats'pelage is sere and dull, figure is increasingly angular, drinking water quantity increases gradually, the temperament is cranky ,and they fight frequently , when seizeing, they resist violent and accompanied by screaming and bite. After treatment, the rats of low dose group, senior dose group, and captopril group showed mental state better, drinking water quantity decreases gradually, the mood tend to easing, and the pelage is luster gradually.2 Qianyangtongluo prescription impact on the blood pressure of spontaneous hypertensive rats2.1 Blood pressure after modeling before treatmentCompared with the blood pressure of N group (108.00±1.18), M (202.25±1.51), C group (203.75±1.40), L group (211.38±1.61), H group (213.13±2.07) were significantly Increased (P <0.01).2.2 Effects on blood pressure after treatmentBlood pressure of M group (208.75±0.56) compared with N group (109.13±0.79) was significantly higher (P<0.01). Treatment groups compared with the M group were significantly decreased (P <0.01). Pairwise comparison among C group (112.25±0.92), L group (153.63±1.03) and H group (147.75±1.06) was significantly different (P <0.01).3 Qianyangtongluo prescription impact on the left ventricular mass index (LVMI) of hypertensive ratsM group LVMI (2.63±0.04) was significantly higher than that of N group (1.19±0.07) (P <0.01). After six weeks'treatment, compared with the M group, LVMI of L group (2.48±0.04) and H group (2.42±0.04) decreased significantly (P<0.05), C group and M were not significant difference (P> 0.05).4 Qianyangtongluo prescription impact on the morphology of myocardial tissue of hypertensive ratsThe myocardial cells of N group were normal size, arranged in neat, compact, distribution of muscle fibers were bundle, and nuclear fission is not obvious. The cardiac myocyte of M group was hypertrophy, interstitial hyperplasia, and increased muscle fibers arranged in disorder. After treatment, the myocardial cells of C group arranged neatly, compared with M group, the myocardial fibers decrease slight, and we can see the rupture. The myocardial cells of L Group neatly arranged cells are Bundle distribution; the myocardial fiber thickening is not obvious, with a small amount of fracture. The cells of H group close to the normal form of N cells.5 Qianyangtongluo prescription impact on catecholamine (adrenaline, norepinephrine) in plasma of hypertensive rats5.1 The effects on adrenaline in plasmaCompared with the N group (4.55±0.46), adrenaline content of M group (15.26±0.87) was significantly higher (P<0.01). After treatment, compared with M group, C group (9.28±0.58), L group (8.82±0.53), and H group (9.57±0.63) were significantly lower (P<0.01), but no significant difference among three groups (P>0.05).5.2 The effects on norepinephrine in plasmaCompared with N group (9.60±0.58) the norepinephrine content of M group (25.12±1.55) significantly increased (P < 0.01). After treatment, compared with M group, C group (20.94±1.59), L group (15.27±1.59) and H group (15.41±1.26) were significantly reduced (P < 0.01), the effect of L group and H group is better than C group (P < 0.05), no difference between L group and H group (P > 0.05).6 Qianyangtongluofang prescription impact on expression of ET receptor protein of hypertensive rats6 Qianyangtongluo prescription impact on expression of ET receptor protein of hypertensive ratsImages show large yellow area means the expression is obvious, ET receptor expression of N group is normal; the yellow zone is not obvious. ETRa and ETRb receptor expression of M group enhance obviously, the yellow regional was wide distribution, high density. After treatment, the expression of C group, L group and H group decreased by different levels, the distribution density of yellow region was sparse.The results of average light density statistical show that M group rats ETRa expression was significantly higher than N group(P < 0.05). After the treatment, compared with the M group, C group, L group, H group was significantly lower (P < 0.05), and L, H group is better than C group (P<0.05).M group rats ETRb expression was significantly higher than N group (P < 0.05). After the treatment, compared with the M group, C group, L group, H group was significantly lower (P < 0.05), and H group is better than C, L group (P < 0.05).7 Qianyangtongluo prescription impact on molecular expression of Angâ…¡receptor (AT1,AT2) of hypertensive ratsThe expression of AT1 of M group (0.478±0.001) is increased significantly compared with N group (0.133±0.002) (P<0.05). After treatment, compared with M group, C group (0.261±0.009), L group (0.357±0.002) and H group (0.265±0.003) reduced signicantly (P<0.05), the H group and C group was lower than L group (P<0.05), H group and C group no difference (P>0.05)The expression of AT2 in M group (0.428±0.004) was significantly higher than N group (0.101±0.001) (P<0.05). After the treatment, compared with the M group, C group (0.248±0.005), L group (0.342±0.012), H group (0.257±0.007) was significantly lower (P<0.05), H group, and C group was lower than L (P<0.05), no difference between H group and C group (P>0.05)8 Qianyangtongluo prescription impact on ET and NO in plasma of hypertensive ratsThe content of ET of M group (269.51±4.83) was significantly higher than the N group (236.40±4.56) (P<0.05). After the treatment, compared with the M group, the content of ET of C group (255.30±3.99), L group (245.99±4.80) and H group (244.42±5.25) decreased significantly (P<0.05).The content of NO in M group (27.15±8.35) was significantly lower than the N group (39.38±10.26)(P<0.05). After the treatment, compared with the M group, C group (36.74±9.77), L group (37.30±7.72), H group (37.41±9.61) was significantly higher (P<0.05). Pairwise comparison among the three groups show no significant difference (P>0.05).9 Qianyangtongluo prescription impact on Angâ…¡in plasma of hypertensive rats The content of Angâ…¡of M group (221.51±2.12) was significantly higher than the N group (142.44±2.12) (P<0.05). After the treatment, compared with the M group, C group (147.25±1.96), L group (161.25±2.18), H group (144.06±1.87) was significantly lower (P < 0.05), and C , H group is better than L group(P < 0.05).Conclusion:1 Qianyangtongluo prescription has a good effect in liver yang left ventricular hypertrophy, and there is a certain dose-effect relationship.2 Qianyangtongluo prescription has the side of lower LVMI, left ventricular hypertrophy, myocardial remodeling to prevent and reduce myocardial fibrosis.3 Qianyangtongluo prescription have good effect on lower blood pressure and left ventricular hypertrophy, this may be achieved by reduced catecholamines, angiotensin receptor, endothelin receptor, ET and Angâ…¡levels and increased NO content.