Basic And Clinical Research Of Jianpitiaozhi Formula In Hyperlipemia

Objectives1. Basic research:The research adopted the method of feeing the polipoprotein E gene knockout mice with high-fat diet to built the method of hyperlipernia and atherosis. Adopted themodel group as the control group; observed the influence of the high, medium, low dose of the Jianpitiaozhi formulaand the simvastin on TC、TG、HDL-C and LDL-C, on the same time, observe and comepare the pathomorphology of the AS in the Aortic by He staining, and the positive expression of the aortic arch on MMP-9, NF-κB and CD68 of ApoE knockout mice by immunohistochemistry.2. Clinical research:The research choosed patients with hyperlipidemia common clinical as research subjects and adopted the simvastatin dispersible tablet as the control group, observed the influence of the Jianpitiaozhi formula on the general situation, blood lipid level, hepatorenal function and vascular inflammation of the hyperliperia patients, and the clinical effect.Methods1. Basic research:Adopted forty-two 8-week apolipoprotein E gene knockout mice. Half were females and half were males. Fed them with high-fatdiet for four weeks. And then chose ten8-week normal C57BL/6J mice with the identical genetic background and feeding them with SPF normal feedstuff(Half were females and half were males).Fed them on the same time and choose two rats (half were females and half were males) from each kind of rats, compare the the blood fat (TG, TC, LDL-C and HDL-C) and the pathological on the aortic arch to prove the hyperlipernia and As model after four weeks. After ensure the model is success divided the remaining 40 12-week ApoE mice into five groups, with eight in each group, and named them as the high-dose TCM group, the medium-dose TCM group, the low-dose TCM group, the simvastatin Western medicine group and the model group, respectively. Gavaged them with high-dose TCM, medium-dose TCM, low-dose TCM, simvastatin and isodose purified water, respectively. The gavage dose was calculated by the conversion algorithm of the body surface area. The high-dose TCM group, the medium-dose TCM group and the low-dose TCM group were gaveged with 6.08g/kg、3.04g/kg and 1.52g/kg respectively. The simvastatin group is gavaged by simvastatin on 5m/kg, the model group and the C57BL/6J rats are gavaged by isodose purified water with the other group. All the groups are gavaged once a day and continue gavaging for six weeks.At the same time the ApoE mice were fed with high-fat feedstuff. This measure is to ensure the formation of atherosclerotic plaques, as well as the determination of the drug’s preventive treatment. And the C57BL/6Jrats were fed with the normal food as theBlank control group. After the mice were treated with the above stated formula for six weeks, the blood was fetched from the eyeball artery to observe the blood fat (TC、TG、HDL-C and LDL-C) changes. Then Fetched the aortic arch of the rats to observe the plaque area and the positive expression in the He dyeing, and observe the expression of MMP-9, NF-κB, and CD68 byimmunohistochemistry.2.Clinical research:By the randomized control method. The hyperlipernia patients were treated in the outpatient department of No. 2 Hospital Affiliated to Traditional Chinese Medicine University of Guangzhou and the wards (including Dede Road Headquarter, Fencun Branch and Ershadao Branch) from July 2013 to June 2015 were divided into the test group and the control group randomly. The patients in the test group took the spleen tonifying and liquid regulation formula particles;while the patients in the control group took dispersible tablets of simvastatin (manufactured by Guangzhou Nanxin Pharmaceutical Co. Ltd.). The dose amount for both was 20mg/d and the medication lasted for 30 days. Patients underwent physical check and blood test before and after taking the corresponding medicine so as to observe the blood fat level, the hepatorenal function level, TCM syndrome integral and the expression level of IL-6, MCP-1 and SOD.Results1. Basic research:After the 8-week ApoE knockout mice were fed with the high-fat feedstuff for ten weeks, TC、TG、LDL were increased and HDL were decreased. And the difference was statistically significant (P< 0.05). The arch of the aortic has appreared intimal thickened and the atherosclerotic plaques by the He observed. On the background of the conditions of high-fat diet, after each groups were gaveged for 6 weeks, Compared with the model group, the TC、TG、HDL-C andLDL-C of the TCM high-dose, medium-dose, low-dose groups and Simvastatindid not register significant decrease (P>0.05). But bythe He dyeing and immunohistochemistry in the aortic arch of the rats, compared with the model group, all the groups of TCM can reduce the plaque area and reduce the expression of MMP-9, NF-KB, and CD68 (P<0.01). the Highest effectiveness is the medium-dose of TCM and it is more effective than Simvastatin (P<0.01).2. Clinical research:According to the Severe patients with elevated LDL-C, both simvastain(20mg/d) and the Jianpitiaozhi formula could reduce the level of the TC、LDL-C、nonHDL -C and ApoB (P<0.05).The remaining indicators were not statistically different for each group (P>0.05).And the Jianpitiaozhi formulacould reduce the level of La(p) and increase the level of ApoAl(P<0.05).According to the mild patients with elevated LDL-C, the Jianpitiaozhi formulacould reduce the level of La(p) and increase the level of ApoAl (P<0.05). The remaining indicators were not statistically different for each group (P>0.05). The result suggests that both drugs have comparable efficacy by the results consistent baseline after treatment (P>0.05). In terms of the inflammatory factor expression, the Jianpitiaozhi formulawas superior toSimvastatin as to the expression level of IL-6and MCP-1 (P>0.05). But SOD was reduced in the simvastain group (P<0.05).In the score of Traditional ChineseSymptoms, the Jianpitiaozhi formulahas difference statistical significance to theSimvastatin (P<0.05).Conclusion:The main object of the research is Jianpitiaozhi formula by the Clinical Experience of author’s tutor. In the basic research, according to feed the ApoE mice with high-fat diet to built the method of Hyperlipemia and Atherosclerosis. And intervene the successful model mice by high-dose TCM, medium-dose TCM, low-dose TCMand Simvastatin. The compared with the model group, research the influencesin lipid levels and plaque of Jianpitiaozhi formula. In the clinical research, Jianpitiaozhiformula also get satisfactory clinical efficacy.By the result the research can summarize the conclusion as follow:1. Basic research:According to the ApoE mice which are feed with high-fat feedstuff for ten weeks and gaveged for 6 weeks, Both TCM high-dose, medium-dose, low-dose groups and Simvastatin could notimprove blood lipid levels. But on the influences of Atherosclerosis, all the groups of TCM can reduce the plaque area and reduce the expression of MMP-9, NF-KB, and CD68, reduce the degradation of extracellular matrix, inhibit the inflammatory response, improve plaque components, reduce macrophage accumulation, and thus play a role in stabilizing the plaque. theHighest effectiveness is the medium-dose of TCM and it is more effective than simvastatin. Sorted them by the pros and cons of influence is the medium-dose of TCM, high-dose of TCM andlow-dose of TCM.2. Clinical research:Compared with Simvastatin, Jianpitiaozhi formula can improve the clinical symptoms effectively, and control the level of TC、TG、LDL、nonHDL-CD、ApoBin the equivalent effect with Simvastatin to the Severe patients with elevated LDL-C. It can prompt that Jianpitiaozhi formula targeted control efficacy threshold for patients with hyperlipidemia. At the same time, Jianpitiaozhi formula can reduce the level of La(p) and increase the level of ApoAl to control of risk factors in atherosclerosis. In terms of the inflammatory factor expression, SOD was reduced in the simvastain group. Jianpitiaozhi formula can increase the expression of SOD but it needs more samples do further research.