| Atherosclerotic cardiovascular disease(ASCVD)is a group of ischemic diseases based on atherosclerosis with common risk factors,pathological characteristics and pathological process,including coronary heart disease,atherosclerotic stroke and peripheral vascular diseases.The morbidity and mortality of ASCVD are high,especially in recent years.It has become a major disease endangering human health,and it tends to occur in young and middle-aged people.Different forms of ASCVD diseases are a serious threat to human health,so it is of great significance to seek reliable and effective drugs for the prevention and treatment of ASCVD.The traditional prevention and treatment of ASCVD by regulating blood lipids has limitations under certain conditions,and attention has been paid to the combination with anti-inflammatory treatment of ASCVD in recent years.Traditional Chinese medicine(TCM)has advantages in the treatment of ASCVD-related diseases:there is no unified TCM treatment plan for ASCVD,and ASCVD can be classified into the category of"pulse arthralgia" and "collateral disease".A large number of research results show that activating blood circulation and removing phlegm-turbid drugs with blood circulation,promoting blood circulation,removing phlegm and turbid phlegm has a better effect in the treatment of ASCVD caused by hyperlipidemia.And the TCM for promoting blood circulation and removing blood stasis has anti-inflammatory effect,can play a role in the treatment of ASCVD from the way of anti-inflammation,and can play a good supplement when the effect of western medicine in reducing blood lipid in the treatment of ASCVD diseases is limited.Statins are the basic drugs to control the level of blood lipids and prevent and cure ASCVD in clinic,but for patients with familial hereditary hypercholesterolemia and statin intolerance,or those who take high-dose statin intensive therapy but have no obvious effect on reducing blood lipid levels,the therapeutic effect of statins has some limitations and needs to be used in combination with different drugs.Curcumin is the main active ingredient of curcuma and curcuma aromatica in promoting blood circulation and removing blood stasis.It has been proved to have a good therapeutic effect in the treatment of tumor,cardiovascular,immune system and other diseases.Curcumin has the pharmacological effects of anti-inflammation,antioxidation and hypolipidemia,and curcumin has low toxicity,so it has a broad prospect in the development of new drugs for the treatment of ASCVD.Through the combined use of statins and curcumin,to observe whether the combination of the two drugs can better inhibit the progression of atherosclerotic plaque and reduce the pathological damage of tissues and organs.The first section:Experimental study on the prevention and treatment of aortic plaque in atherosclerotic mice by atorvastatin,curcumin and the combination of curcumin and curcuminObjective:Different administration schemes are given to observe the degree of atherosclerotic plaque and inflammatory infiltration of macrophages in aortic root plaques in mice.To evaluate the effect of different treatment schemes on inhibiting the progression of atherosclerotic plaque.Methods:SPF grade C57BL/6J and apolipoprotein E knockout(ApoE-/-)male mice were used,C57BL/6J mice were fed with normal diet as normal control C57 group,and ApoE-/-mice were fed with high fat diet to establish atherosclerotic model.At the same time,different intervention drugs were given by intragastric administration,which were divided into model group,atorvastatin group,curcumin group and statin+curcumin group.Oil red O staining was used to observe the occurrence of aortic plaque in each group.Hype staining and Masson staining were used to observe the severity of plaque area located at the aortic sinus of the aortic root.The expression of macrophage marker CD68 in aortic root plaque was observed by immunohistochemical staining.Results:(1)There was no difference in body weight among different groups.(2)The results of Oil Red O staining showed that compared with the model group,the treatment group did not reduce the plaque area and the proportion of total aortic area,but it was better than that of different drugs alone.The combination of the two drugs had a certain advantage in reducing the proportion of plaque to aortic area at the 6th week,but this advantage disappeared after 12 weeks.Compared with before and after treatment in this group,atorvastatin group performed relatively well in controlling the changes of aortic atherosclerotic plaque area and plaque area in this group.Although the plaque area and proportion in this group showed an upward trend at the 12th week,but this growth trend was relatively slower than that in the curcumin group and the two drugs combination group.(3)For the treatment of aortic root plaque,compared with the model group,the plaque area of the three regimens was reduced after 12 weeks(P<0.05),and curcumin and the combination of curcumin and curcumin also played a significant role in reducing the proportion of plaque(P<0.05).The combination of statin and curcumin first showed a tendency to inhibit the progression of aortic root plaque in 6 weeks.The effect of long-term use of curcumin on the continuous reduction of plaque area in this group was more obvious(P<0.05).(4)The results of CD68 immunohistochemical staining showed that there was obvious brown CD68 positive expression area in the plaque area of the model group.Compared with the model group,there was no significant difference in the positive expression area of CD68 and the percentage of positive expression in the total plaque area among the three groups after 6 weeks and 12 weeks,but the effect was the most obvious in both the statin+curcumin group and the treatment group in terms of reducing the positive area of CD68 or the proportion of CD68 positive area in the plaque area,and there was a tendency to reduce the positive expression area of CD68 at 6 weeks.After 12 weeks,the expression area of CD68 in this group was significantly lower than that in the model group(P<0.05).The positive expression area of CD68 in the 12th week of the three treatment groups showed a certain downward trend compared with the results of the 6th week in this group,but the atorvastatin group played a poor role in reducing the proportion of CD68 positive area.Curcumin group and the combined use of curcumin group and the two drugs combination group had a certain advantage in continuously controlling the proportion of CD68 expression.Conclusion:The combination of curcumin and atorvastatin is more effective than atorvastatin or curcumin alone in reducing the area of aortic root plaque.Curcumin combined with atorvastatin can significantly inhibit the progression of atherosclerotic plaque in aortic root by reducing the infiltration of inflammatory cells in the plaque and reduce the damage of inflammation to cardiovascular and related tissues.The combination of the two drugs can play a better role in anti-ASCVD.The second section:Effects of atorvastatin,curcumin and the combination of two drugs on lipid metabolism-related tissues in atherosclerotic miceObjects:Different administration schemes were given to observe the pathological changes of liver and the morphological changes of white adipose tissue in mice under different administration schemes,and to evaluate the different effects of different treatment schemes on tissues closely related to lipid metabolism.Methods:H&E staining was used to evaluate the pathological changes and inflammatory injury of the liver.The morphological changes of white adipose tissue adipocytes were observed by H&E staining,and the expression of uncoupling protein 1(UCP-1),a marker of white adipose tissue browning,was observed by immunohistochemical staining to evaluate the degree of white adipose tissue browning activation.Results:(1)The pathological changes of liver were observed by H&E staining.At the 6th week,the effect of each group on liver tissue was not obvious.After 12 weeks of administration,the inflammatory injury of liver and the number of lipid droplets were improved and reduced to some extent.However,the protective effect of liver tissue in the curcumin group and the combination group was better than that in the atorvastatin group,especially in the statin+curcumin group.The staining results after 12 weeks showed that the liver morphology and structure of the curcumin group were similar to those of the C57 group;(2)White adipose tissue H&E staining showed that there was no significant difference in adipose tissue between the 6th week group,the size of adipocytes was relatively consistent,and the volume of model adipocytes did not increase significantly.However,in the 12-week model group,the volume of adipocytes increased to a certain extent,and the tissue was relatively looser.After 12 weeks of administration,the volume of fat vacuoles in the three groups was smaller than that in the model group to a certain extent.In particular,a large number of reduced adipocytes appeared in the curcumin group and the statin+curcumin group;(3)The results of UCP-1 immunohistochemical staining showed that the white adipose tissue of the three groups showed browning,but there was no difference in the average optical density of UCP-1 positive expression.Conclusion:The combination of curcumin and atorvastatin can protect the structure and morphology of hepatocytes more obviously than atorvastatin alone,and can obviously control the inflammatory injury and steatosis of hepatocytes.The supplementary use of curcumin can also reduce the volume of adipocytes and reduce the necrosis of adipose tissue. |
PDF Full Text Request