Study On The Efficacy And Mechanism Of Qima Capsule In Improving Intimal Thickening Of Carotid Artery

ObjectiveTo observe the effect of Qima capsule on Carotid Atherosclerosis(CAS)in New Zealand rabbits and its effect on serum lipid level,inflammatory factors and immune cells.Meanwhile,the clinical efficacy and safety of Qima capsule combined with atorvastatin calcium tablet in improving carotid artery intimal thickening in CAS patients with qi deficiency and phlegm turbidity were observed.In order to reveal the mechanism of Qima capsule to improve carotid artery intimal thickening.Method1.35 New Zealand rabbits were randomly divided into control group,model group,Qima capsule low-dose group(1.5g/kg),Qima capsule high-dose group(3g/kg)and atorvastatin group(2.5mg/kg),7 rabbits in each group.The control group was fed with normal feed,and the other groups were fed with high-fat feed(50g·d-1)for 18 weeks.The model group and each treatment group were given bovine serum albumin injection on day 1,3 and 5 to construct the rabbit CAS model.Starting from the 13th week,each treatment group was given corresponding drug gavage therapy,while the control group and the model group were given equal volume distilled water gavage for 6 weeks.After 18 weeks,each New Zealand rabbit continued to give ordinary feed 2 weeks,serum of rabbit was extracted to detect the serum lipid leve(TC,TG,LDL-C,HDL-C),serum APN,serum inflammatory cytokines(MCP-1,NLRP3,TNFa,IL-10).Then,the experimental rabbits were sacrificed and bilateral carotid arteries were taken to observe the histological changes of carotid arteries in rabbits and the factors related to vascular lesions in carotid tissues were determined(VCAM-1,ICAM-1,PECAM-1,MMP-9,TGF-β1),Meanwhile,the immune indexes of T lymphocytes(CD4+CD25+Foxp3+/CD4+CD25+,CD4+CD25+/CD4+)were detected in thymus and spleen of rabbits.2.Choose between January 2016 and March 2017 in the second hospital of guangdong province medical outpatient or hospitalization and meet eligibility criteria of the qi deficiency type phlegm turbidity CAS patients 105 cases as the research object,were randomly divided into Chinese medicine group and western medicine combined treatment group,which fall off 6 cases,actual into 99 cases,groups of 33 cases,were given atorvastatin calcium,Qima capsules and atorvastatin calcium tablets combined with Qima capsules.Carotid artery color doppler ultrasonography was used to detect the IMT value of the patients’carotid artery internal middle membrane thickness(IMT),and to compare the changes of serum lipid levels(TC,TG,LDL-C,HDL-C),serum APN,ox-LDL,LOX-1,ALT and AST levels before and after treatment in each group.At same time,The adverse reactions of the patients during medication were observed.Result1.Changes of carotid artery intima tissue morphology in New Zealand rabbits:the carotid artery structure of the rabbits in the control group was clear,theintima was smooth,and there was no change in lumen.Compared with control group,it could be observed that carotid artery showed typical CAS pathological changes in model group.The intima of the arteries was thicken,and the surface of the lumen wasrough.In addition,there were a lot of amorphous substances and necrotic substances which deposited in lumen,and the surrounding lumen was narrowed.Compared with the model group,the thicknessof carotid intima was significantly reduced in the treatment groups.The surface of the lumen was smooth,and only a part of the lumen was found to be surrounded whih thin layer of lipid plaque.Interestingly,the improvement of pathological morphology was more remarkable in high doseof the Qima capsule group when compared withhigh doseof the Qima capsule group.2.Changes of serum lipid and related factors in New Zealand rabbits with carotid atherosclerosis:Compared with the control group,the levels of serum TC,TG,LDL-C,MCP-1,NLRP3 and TNF-ain the model group were significantly increased,while the levels of serum APN and IL-10 were significantly decreased,and the mRNA expressions of ICAM-1,VCAM-1,PECAM-1,MMP-9 were significantly increased,while the mRNA expressions of TGF-β1 was significantly decreased(P<0.05).In addition,theimmune in rabbit thymus and spleen tissueindex CD4+CD25+Foxp3+/CD4+CD25+was significantly decreased(P<0.05).Compared with the model group,the serum levels of TC,TG,LDL-C,MCP-1,NLRP3,TNF-ain the high and low dose group of Qima capsule of atorvastatin calcium group were significantly decreased(P<0.05),the serum levels of APN,IL-10were significantly increased(P<0.05),the mRNA levels of ICAM-1,VC AM-1,PEC AM-1 and MMP-9 in rabbit carotid artery were significantly decreased(P<0.05)and the mRNA level of TGF-β1 was significantly increased(P<0.05).Meanwhile the immunological indexes CD4+CD25+Foxp3+/CD4+CD25+were significantly increased in thymus and spleen tissues of rabbits(P<0.05).The high-dose Qima capsule has a more obvious regulatory effect on various indicators,and the difference is statistically significant(P<0.01).In addition,the level of HDL-C and CD4+CD25+/CD4+in each group have no significant difference(P>0.05).3.Results of clinical research:Before treatment,the serum levels of TC、TG、LDL-C、HDL-C、APN、ox-LDL、LOX-1、ALT and AST had no statistically difference between all the groups(P>0.05).After 12 weeks treatment,the serum levels of TC,TG,LDL-C,ox-LDL and LOX-lwere decreased at different degrees(P<0.05),while the serum levels of HDL-C and APN were significantly increased(P<0.05).Moreover,the combined treatment group had the most significant effect,followed by the western medicine group.The serum levels of ALT and AST of the three groups was still within the normal reference range,but the ALT level in the western medicine group was significantly higher(P<0.05),and theserum ALTand AST levels were significantly lower in the combination treatment group(P<0.05).There was no significant difference in ALTand AST level before and after treatment in the traditional Chinese medicine group,and no significant difference inAST level before and after treatment in the western medicine group(P>0.05).At the same time,no adverse reactions were found during the treatment.ConclusionAnimal experiments showed that Compound Qima capsule can improve carotid artery intima thickening in CAS New Zealand rabbits,regulate blood lipid metabolism,inhibit inflammation,and regulate immune function.Further verification through clinical trials,patients with Qima capsule effectively regulate lipid metabolism,inhibit the body’s inflammatory response,improve the carotid artery endothelial injury,reduce IMT,its mechanism may be related to accelerate the metabolism of lipids and reducing blood lipid levels,inhibit the body’ s inflammatory response,regulate the body’s immune function and promote immune function recovery.In addition,the safety of drug clinical application is good,and within a certain range,its therapeutic effect may have a dose-effect relationship,worthy of clinical promotion and application.