| Objective: To reseach the treatment effects and its mechanisms of genistein on atheroselerosis induced by high cholesterol diet with intraperitoneal injection of low dose of trichlorfon in Sprague-Dawley rats.Which may futher elucidate the possible mechanism of anti-atherosclerosis of genistein by biology-chemical methods.Methods:Sprague–Dawley rats were randomly divided into seven groups.The three groups were the ehicle control(1ml·kg-1·day-1),genistein control( 5mg·kg-1·day-1) and simvastatin control( 5mg? kg-1? day-1) were fed with normal diet;the other four groups were the vehicle control(1ml·kg-1·day-1), low dosage genistein (0.5mg·kg-1·day-1), high dosage genistein (5mg·kg-1·day-1 and simvastatin(5mg·kg-1·day-1) were fed with hypercholesterolemic diet (HCHL) and Tichlorfon(10mg·kg-1·day-1).The contents of triglyceride(TG),total cholesterol(TC),high density lipoprotein holesterol (HDL-C),low density lipoprotein cholesterol(LDL-C),glucose(GLU),C- reactive protein(CRP) of serm in rats were detected on the0,4 and 8th after treatment. The amount of total cholesterol,triglyceride,HDL-cholesterol, LDL-cholesterol and CRP in the blood were determined by using an automatic analysis technique on a chemical analyzer from Roche Diagnostics(Roche analyzer H7600, Germany). Atherosclerotic index (AI) was calculated by the formula:AI =(TC-HDL-C) /HDL -C.GLU was measured by Yicheng Blood glucose meter.Ntric oxide (NO), paraoxonase(PON1), malondialdehyde (MDA) were measured on the 4 and 8th; Acetylcholine esterase(AchE) of blood was measured and the histological changes in aortic arch and liver were observed by HE stain on the 8th.Select the heart and weighted it to compute the index number PON1 activities were detected by spectrophotography.The amount of PON1 was determined by taking the absorbance at 270nm.The level of malondialde-hyde (MDA) was monitored by thiobituric acid reaction (TBA).Total NO was measured by Griess reagent.The amount of NO was determined by taking the absorbance at 546nm.The protein levels of eNOS were monitored by immunohistochemistry. Hydroxyamine method was used to measure AChE activity.Results:(1)On the 4 th,8th-week after treatment, the levels of TC,HDL-C,LDL-C and the value of AI in four HCHL+Tichlorfon groups were significantly higher than those in three normal diet groups (P<0.05,P<0.01 or P<0.001),but the ratio of HDL-C and TC were significantly lower in groups with HCHL+Tichlorfon than those in groups with normal diet (P<0.05,P <0.01 or P<0.001). Simvastatin and genistein can lower the levels of TC,HDL-C,LDL-C , the value of AI, and raise the ratio of HDL-C and TC.(2)Simvastatin and genistein groups decreased significantly(P<0.05 or P<0.001) the level of GLU in atherosclerotic rats.(3) High dosage genistein and Simvastatin decreased significantly(P<0.05 or P<0.01 ) the level of MDA in atherosclerotic rats .(4) High dosage genistein and Simvastatin decreased significantly the level of CRP in the atherosclerotic rats(P<0.05).(5)On the 4th,8th-week after treatment, the levels of nitric oxide of the four groups with HCHL+ Tichlorfon were significantly higher than those of nomal diet groups (P<0.01). Compared with the model control group with HCHL+Tichlorfon,there was no significant difference in the groups genistein and simvastatin groups with HCHL+Tichlorfon(P>0.05)(6) Genistein and Simvastatin increased significantly(P<0.05 or P<0.01 ) the content of PON1 among the atherosclerotic rats in a dose-dependent manner.(7)Aortic histomorphology changes were observed by HE staining.The damages of the aortas in genistein and simvastatin groups were lesss severe than that in model group.(8)Genistein increased the expression of eNOS in arterial vessels and protected the blood vessel so as to inhibit the formation of atherosclerosis.Conclusion: Genistein significantly suppress the development of atherosclerosis induced by HCHL+Tichlorfon and improve the histopathological changes. These effects may attribute to reverse of dyslipidemia, inhibition of lipid peroxidation, lowering of CRP,regulation of NO, eNOS and PON1 system.
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