Effect Of Modified And Enriched Lingdan On Early Arterial Cirrhosis Of Diabetic Rats

ObjectivesTo explore the effects of activating blood and dissolving stasis based formula add-subtract HLXLD to atherosclerosis on Wistar rat with diabetic atherosclerosis through measuring arterial pathologies,blood lipid,high-sensitivity C-reactive protein (H-CRP). To study the possible intervention and mechanism in respect of caveolin-1(Cav-1),NF-κB and related gene expression.Try to discuss the feasibility of Cav-NF-κB signaling pathway.Methods40 male Wistar rats were randomly divided into blank cntrol group (CON)(10) and experimental group(30).All rats were fed adaptively for 1 week and then the experimental group were given intraperitoneal injection of STZ to copy diabetic model.30 successfully modeled rats with RBG(radom blood glucose)= 16.9mmol/L further randomly and evenly divided into three group:diabetic atherosclerosis control group(AS), atorvastatin group(TD) and Chinese medicine group(ZY).Two days after diabetes model establishment,AS,TD and ZY groups were given VitaminD by savage for 3 days and fed with high fat feed(3% cholesterol,0.5% bile acid,0.2% PTU,5% glucose,10% oil,81.3% basic feed)in order to establish atherosclerosis model.While the CON group remained basic feed during the 14-week experiment. At the end we measured CHO, TG, HDL-C, LDL-C,VLDL,H-CRP in blood; observed arterial pathologies under optical microscope;tested Cav-1,NF-κB and related gene expression in aorta with WB and PCR method respectively.Results1. Content of serum CHO, TG, LDL-C, VLDL,H-CPR in AS group rats increased obviously. Intimal thickenings,smooth muscle fibers proliferation and lipid plaque formation could be observed in aorta HE-stained slice under optical microscope.2. Compared with AS group, the level of CHO, TG, LDL-C,VLDL in ZY group rats decreased significantly(P<0.01)while HDL-C increased (P<0.05).Compared with TD group,LDL-C content of ZY group rats descended remarkablely(P<0.01).3. Compared with AS group, the content of H-CRP in ZY and TD group rats both decreased significantly(P<0.01).Compared with TD group,there was a notable descending of H-CRP content in ZY group rats(P<0.01).4. Compared with AS group, the arterial pathological condition is much better in ZY group rats.still not as well as the TD group rats.5. Compared with CON group,the protein expression and gene transcription of cav-1 in AS group rats descended while NF-κB increased dramatically(P<0.01).The inhibitory and reserve effect could be observed both in ZY and TD group rats.Furthermore,the NF-κB protein expression in ZY group descended more than TD group(P<0.01).Conclusions1. High-fat fed combined with VitaminD can successfully replicated atherosclerosis model in Wistar rats.2. Add-subtraction HLXLD can regulate serum lipid metabolism of diabetic atherosclerosis model rats.3. Add-subtraction HLXLD can improve the microinflammatory state of diabetic atherosclerosis model rats.4. Add-subtraction HLXLD has a positive effect of anti-atherosclerosis on diabetic atherosclerosis model rats.5. Add-subtraction HLXLD can up-regulate the protein expression and gene transcription of cav-1 while down-regulate those of NF-κB in diabetic atherosclerosis model rats. The possible anti-atherosclerosis mechanism of add-subtraction HLXLD lies that it accelerates reverse transportation of cholesterol and inhibites inflammatory response by promoting generation of cav-1 on cytomembrane,and then transmit the signal into nucleus to inhibite NF-κB activation so as to block the downstream pathways.