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The Efficacy And Mechanism Of Xuezhikang For Renal Protection

Posted on:2019-05-10Degree:DoctorType:Dissertation
Country:ChinaCandidate:M DingFull Text:PDF
GTID:1364330572952973Subject:Department of Cardiology
Abstract/Summary:PDF Full Text Request
Hyperlipidemia is an independent risk factor for cardiovascular and cerebrovascular diseases.With the improvement of living standards,more and more patients with hypertension,diabetes mellitus and kidney injury,kidney injury and abnormal lipid metabolism aggravate each other.So I hope to find drugs that have little effect on kidney while lipid-lowering therapy.Xuezhikang contains many active ingredients,so how does it affect the kidney? Domestic research suggests that Xuezhikang has the function of protecting kidney.At present,there are few systematic research data,and no relevant research and data published abroad.Objective:To observe the effects of Xuezhikang on inflammatory factors and oxidative stress indicators while lowering blood lipid,and to reveal the protective effect and mechanism of Xuezhikang on renal function,through animal experiments and clinical studies.Methods:Firstly,we conducted a clinical trial in which a total of 100 dyslipidemic patients with low to moderate cardiovascular risk were recruited and randomly assigned to receive either Lovastatin(n = 50)or Xuezhikang(n = 50)for 40 weeks.Collect fasting blood from patients to do the detection of the serum lipid profile,the safety profile,renal function profile and hs-CRP at 0,12,24,and 52 weeks.After that,in order to further explore the effect of Xuezhikang on kidney and the mechanism,a rat hyperlipidemia model combined with kidney injury was established.Forty SD rats were randomly divided into normal control group,hyperlipidemia group(model group),Xuezhikang group and lovastatin group.The rats of the model group and 2 treatment groups were fed with high cholesterol diet rich in vitamin D3.After successful modeling,the two treatment groups were given drug therapy for 6 weeks.24-hour urine samples of rats were collected.Then the rats were executed to collect blood samples and kidney tissue for Detection the following parameters: the serum lipid profile,renal function indexes,inflammatory factors,oxidative stress indexes of kidney and renal histomorphology.Finally,the data were analyzed statistically.Results:In the clinical trial part,the serum low-density lipoprotein-cholesterol(LDL-C),total cholesterol(TC)and triglyceride(TG)levels of lovastatin and Xuezhikang groups were significantly lower than those of baseline(P < 0.01)at 12 weeks after treatment,and there was no significant difference between the two groups(P > 0.05).At 24 and 52 weeks,the decrease of the above indexes was smaller than that at 12 weeks,but the measured values of the above indexes were still significantly lower than those at baseline(P < 0.01).The serum high-density lipoprotein cholesterol(HDL-C)levels in Xuezhikang group increased at 12,24 and 52 weeks compared with baseline(P < 0.01),while HDL-C levels in Lovastatin group decreased at 12,24 and 52 weeks compared with baseline(P > 0.05).There was significant difference between the two groups(P < 0.01).Serum creatinine(Scr)and blood urea nitrogen(BUN)levels decreased slightly at 12,24 and 52 weeks,but there was no significant difference compared with baseline(P > 0.05),and there was no statistical difference between the two groups(P > 0.05).The serum hs-CRP levels in the two groups decreased gradually at 12,24 and 52 weeks,but there was no statistical difference compared with baseline(P > 0.05),and there was no statistical difference between the two groups(P > 0.05).There was no significant changes about serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),creatine kinase(CK)at 12,24 and 52 weeks compared with baseline in the two groups(P > 0.05).Animal experiment: Compared with the normal control group,the levels of LDLC,TC and TG in the model group were significantly higher(P < 0.01).Compared with the model group,the levels of LDL-C,TC and TG in Xuezhikang group and Lovastatin group were significantly lower(P < 0.01);there was no statistical difference between the two groups(P > 0.05).Compared with the normal control group,the HDL-C level in the model group was significantly lower(P < 0.01).Compared with the model group,the HDL-C level in Xuezhikang group was significantly higher(P < 0.01).Compared with the model group,the HDL-C level in the lovastatin group was slightly lower,but there was no statistical difference(P > 0.05).There was statistical difference between the two groups about the HDL-C level(P < 0.01).Compared with the normal control group,the levels of BUN,Scr,urine creatinine(Ucr),uric acid(UA)and 24-hour albuminuria in the model group decreased(P < 0.01).Compared with the model group,the levels of BUN,Scr,Ucr,UA and 24-hour albuminuria in the Xuezhikang and Lovastatin groups decreased(P < 0.01).There was no significant difference between the two groups about the levels of the above indicators(P > 0.05).Compared with the normal control group,the levels of serum TNF-? and IL-6 protein and renal tissue TNF-? and IL-6 mRNA and protein in the model group were significantly higher(P < 0.01).Compared with the model group,the levels of the above indicators in Xuezhikang group and Lovastatin group were significantly lower(P < 0.01).There was no significant difference between the two groups about the levels of the above indicators(P > 0.05).Compared with the normal control group,the activity of SOD and CAT and the content of GSH-px in kidney tissue in the model group were significantly decreased(P < 0.01),and the level of MDA was significantly increased(P < 0.01).Compared with the model group,the activity of SOD and CAT and the content of GSH-px in Xuezhikang group and Lovastatin group were increased(P < 0.01),and the level of MDA was decreased(P < 0.01).There was no statistical difference between the two groups about the levels of the above indicators(P > 0.05).Histopathological findings showed that Xuezhikang and Lovastatin could significantly improve the renal histological damage caused by hyperlipidemia.Conclusion:1.Xuezhikang has similar effects with Lovastatin,while regulating blood lipid,it may reduce the levels of Scr and BUN and downregulate inflammatory reaction in hyperlipidemia patients.2.Hyperlipidemia can induce the increase of urinary protein,serum and urine creatinine,serum urea nitrogen and uric acid in rats.Both Xuezhikang and Lovastatin can reduce the levels of the above-mentioned indexes.3.Also,like Lovastatin,Xuezhikang can downregulate inflammatory reaction in serum and kidney tissue,and downregulate oxidative stress reaction in kidney tissue in hyperlipidemia rats.4.Xuezhikang upregulates the level of HDL?C better than Lovastatin.
Keywords/Search Tags:Xuezhikang, Lovastatin, hyperlipidemia, kidney function, cardiovascular disease, tumor necrosis factor-?, interleukin-6, oxidative stress
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