Effect Of Bushen Jiangya Decoction On Adiponectin Pathway In Rats With High Blood Pressure And Abnormal Glucose And Lipid Metabolism

Literature and Theoretical ResearchClinically, hypertension and abnormal glucose and lipid metabolism are in close contact. They influence each other, increase the incidence of cardiovascular and cerebrovascular disease risk and mortality. They are called as "four quartets" of modern urban people’s death with obesity. The treatment of hypertension and abnormal glucose and lipid metabolism often requires a variety of drug administration. The major of hypoglycemic drugs is glitazones, PPAR gamma agonist which has some adverse effects on the liver, and increasing risk of heart failure. sulfonylurea, biguanides which have hypoglycemic effect at the same time also takes a number of adverse reactions. Statins is currently the most effective of common lipid-lowering drugs for regulating blood lipid, but the long-term use caused liver damage and muscle dissolution, which limits the high dose and long-term use.Chinese medicine treatment of anti-hypertension effect is not satisfactory in patients with moderate or severe hypertension. But it has some irreplaceable advantages in the following aspects, including improvement of symptoms and the quality of life, more smooth blood pressure, reduction of risk events, protection of target organ, prevention of complications. Some scholars believe that the pathogenesis of hypertension with abnormal glucose and lipid metabolism is phlegm dampness, but after a great deal of researches we found that the fundamental pathogenesis is deficiency of the kidney, while heart fire, liver fire, phlegm and blood stasis are just surface condition. The reasons that the basic pathogenesis is deficiency of the kidney mainly has the following several department. First, kidney stores up essence, as the birth of the life. Second, kidney governs water, so the pathogeny of water, turbid and phlegm contribute to the kidney. Third, Because of the physiological changes, deficiency of five zang organs and kidney essence, often are expressed as a physiological deficiency of kidney. Fourth, kidney deficiency is the development stage of glucose and lipid metabolism of hypertension. As long-term consumption can lead to kidney essence loss, involving the kidney yin and kidney yang. Fifth, the deficiency of kidney is adverse drug reactions of anti-hypertension medicine. This is the decisive characteristic of the physiological characteristics and diseases of the kidneys. In addition, clinical observation on the treatment of nourishing kidney with clearing away the heart fire, liver fire is satisfactory. And the traditional Chinese medicine has obvious effect in improving the clinical symptoms and life quality of the patients.Experimental StudyBased on the formation of tonifying kidney therapy, "tonifying kidney anti-hypertension Decoction" is Professor Wang lie’s experience prescription, composed of Rehmannia glutinosa Libosch, Gastrodia elata Bl., Eucommia ulmoides Oliver, Panax notoginseng and so on. This experiment was designed to investigate the effect and gene regulation metabolism of tonifying kidney anti-hypertension decoction on rats with abnormal blood pressure, glucose and lipid metabolism.Objective:To observe the effect of tonifying kidney anti-hypertension decoction on SHR with abnormal blood lipid and blood glucose and explore its effect on adiponectin pathway preliminarily.Methods:40 healthy clean grade 5 week old SHR were randomly divided into the normal diet group and high-fat group. After 8 weeks to set up the model, the high-fat group rats were divided into three groups:model group (blank SHR with abnormal glucose and lipid metabolism), captopril group and tonifying kidney group (tonifying kidney anti-hypertension decoction). The administration of drug continues 8 weeks. Blood pressure was measured 1 times a week, while blood glucose was measured every two weeks. After the treatment of 8 weeks, the rats were killed. Blood glucose, blood lipid and insulin are test. Myocardial tissue sections stained with HE to observe the change of pathological histology of heart. Test Real time quantitative PCR detection of AMPK,PPARa,CPT-1,PI3K,Akt and eNOS mRNA gene expression. Test AdipoRl, AdipoR2,APPL1,AMPK,pAMPK,p38MAPK,PPARaprotein expression in heart tissue with Western blot.Results:(1) Blood pressure:before drug blood pressure of SHR with a high sugar and fat diet had no statistical difference (P>0.05). Blood pressure of groups with a high sugar and fat diet is higher than normal diet (P<0.05). It shows that the model was established. After treatment of 4 weeks, compared with the model group rats, Captopril group lowers blood pressure significantly (P<0.05). After 8 weeks, Captopril group and tonifying kidney group were compared with the model group, the blood pressure was statistically significant (P<0.01). Captopril group was compared with tonifying kidney group with no significant difference.(2) Blood glucose and lipid:Before drug blood glucose of SHR with a high sugar and fat diet had no statistical difference (P>0.05). blood glucose of groups with a high sugar and fat diet is higher than normal diet (P<0.05). It shows that the model was established. After 8 weeks of administration, captopril group and tonifying kidney group were compared with that of model group rats. Captopril group had lower blood glucose trends, but no significant difference (P>0.05), and the results of tonifying kidney group were similar to that of model group.(3) Myocardial histopathology:under an optical microscope:SHR myocardial fibers in rat are thickening, buckling with significant fuzzy boundary. in model group myocardial fibers of rats are swelling and fracture, arranged in disorder. the boundary is not clear and the nucleus is not uniform. There are the junctions between the cells of osteoporosis, visible local infiltration of inflammatory cells, focal necrosis, and atheromatous plaque. Rats in Captopril group significantly reduced the situation, close to normal; tonifying kidney group improved myocardial tissue.(4) In expression of PPARamRNA in the liver, comparison between groups accords with the homogeneity of variance criterion(F=3.519). Compared with SHR group, the model group increased without significant difference; Cato group and Bushen group were decreased (P>0.1, P=0.052). Compared with the model group, Cato group and Bushen group is lower with significant difference (P=0.053, P<0.01). Compared with Cato group, Bushen group decreased without significant difference (P>0.1).In expression of PPARamRNA in the heart, comparison between groups accords with the homogeneity of variance criterion (F=18.508). Compared with SHR group and model group, Cato group and Bushen group increased with significant differences (P<0.01, P<0.01, P<0.05). Compared with the model group, Cato group and Bushen group were decreased with significant difference (P<0.05). Compared with the large group, Bushen group increased without significant difference (P>0.1).The expression of PI3KmRNA between groups accords to the homogeneity of variance criterion (F=21.030). Compared with SHR group, the model group was significantly decreased (P<0.01), Cato group were significantly increased (P<0.01), and kidney group had no significant difference. Compared with the model group, Cato group and Bushen group increased (P<0.01, P=0.058). Compared with Cato group, Bushen group had significant difference (P<0.01).The expression of AktmRNA between groups accords to the homogeneity of variance criterion(F=21.191). Compared with the SHR group and model group, Cato group and Bushen group were significantly reduced (P<0.01). Compared with the model group, Cato group and Bushen group were significantly increased (P<0.01, P<0.05). Compared with Cato group, Bushen group had no significant difference (P>0.1).The expression of eNOSmRNA between groups accords to the homogeneity of variance (F=21.191) criterion. Compared with the SHR group, model group and Cato group have significantly decreased (P<0.01). Compared with the model group, Cato group and Bushen group were significantly increased (P<0,01, P<0.05). Compared with Cato group, Bushen group was significantly decreased (P<0.01).(5) The expression of AdipoRl protein in comparison between groups meets the homogeneity of variance criterion (F=3.186). Compared with the model group, SHR group, Cato group and Bushen group were increased. The model group had significant difference (P<0.01). And Cato group and Bushen group had no significant difference (P=0.091, P>0.1). Compared with the model group, Cato group and Bushen group decreased wirhout significant difference (P>0.1). Compared with the large group, Bushen group was essentially flat without no significant difference (P>0.1).The expression of AdipoR2 protein between groups meets the homogeneity of variance standard (F=3.365). Compared with SHR group, model group, group of Cato and Bushen group increased with significant difference between the model group and the group (P<0.05). Compared with the model group and the Cato group, Bushen group decreased without significant difference (P>0.1).The expression of APPL1 protein between groups meets the homogeneity of variance standard (F=3.716). Compared with SHR group, model group and Cato group increased without significant difference (P<0.05, P<0.01), and Bushen group also increased (P=0.66). Compared with the model group, Cato group, Bushen group and model group increased without significant difference (P>0.1). Compared with Bushen group, Cato group had a decreasing trend without significant difference (P>0.1).In the comparison of AMPK2a protein expression, compared with the group (F=0.165). The four groups had no obvious decrease trend without no significant difference (P>0.1).The expression of pAMPK-2a protein between groups meets the homogeneity of variance standard (F=1.488). Compared with SHR group, the model group and Cato group were higher, without significant difference (P>0.1, P=0.92). Compared with the model group, Cato group and Bushen group decreased without significant difference (P>0.1, P=0.75). Compared with Cato group, Bushen group decreased without significant difference (P>0.1).The expression of MAPKp38 protein between groups meets the homogeneity of variance standard (F=10.251). Compared with the model group, SHR group, Cato group and Bushen group were decreased with significant difference (P<0.01, P<0.01, P<0.05). Compared with the model group, Cato group had a decreasing tendency, and kidney group were increased without significant difference (P>0.1). Compared with the large group, Bushen group increased with significant difference (P<0.05).The expression of PPARa protein between groups meets the homogeneity of variance criterion (F= 1.796). Compared with the model group, SHR group, Cato group and Bushen group increased with significant difference (P<0.05). Compared with the model group, Cato group increased without significant difference (P>0.1). Compared with Cato group, Bushen group decreased without significant difference (P>0.1).Conclusion:(1) Tonifying kidney anti-hypertension Decoction can lower hypertension steadily in hypertension patients with abnormal glucose and lipid and improve blood lipid without affecting glucose。(2) Tonifying kidney anti-hypertension Decoction can reduce hypertension and abnormal glucose and lipid metabolism of myocardial pathological changes to some extent.(3) Tonifying kidney anti-hypertension decoction can down-regulate the PPARamRNA and up-regulated the expression of PI3KmRNA, AktmRNA, eNOSmRNA expression.(4) Tonifying kidney anti-hypertension decoction can down-regulate AdipoRl, AdipoR2, APPL1, p-AMPK2a, PPAR expression, and up-regulation of MAPK p38 expression.(5) Tonifying kidney anti-hypertension decoction has protective effect on SHR associated with cardiac abnormalities in glucose and lipid metabolism. The mechanism may be through the up-regulation of PI3KmRNA, AktmRNA, eNOSmRNA, MAPK p38 expression and down-regulation of PPAR alpha mRNA, AdipoRl, AdipoR2, APPL1, p-AMPK2a, PPAR expression.