| OBJECTIVETo investigate the effect of ATP-binding cassette transporter G1(ABCG1)on blood lipids in atherosclerosis(AS)rats with abnormal glucose and lipid metabolism and the possible regulation mechanism of Ghrelin.METHODSHealthy male Wistar rats were weighed(250±50)g before the experiment.They were randomly divided into 5 groups,namely,group A,B,C,D,and E,that is,high fat group(group B,high fat diet+arterial intimal injury),high glucose group(group C.high fat diet+arterial intimal injury+diabetes),Ghrelin group(group D,high fat diet+arterial intimal injury+diabetes+Ghrelin),rosuvastatin group(group E,high fat diet+arterial intimal injury+diabetes+rosuvastatin),The sham operation group was set as the control group(group A,normal diet),and 10 rats in each group were successfully established after the model was successfully established.After 2 weeks of feeding,group D was given Ghrelin 100 μg·kg-1·d-1(concentration 100 μg/ml)once daily for intraperitoneal injection,and group E was given rosuvastatin 100 μg·kg-1·d-1(concentration 100 μg)./ml),once a day,the other groups were given normal saline 100 μg·kg-1-d-1,(concentration 100 μg/ml),once a day intraperitoneally,after 6 weeks of intervention.Weighing,measuring blood sugar before taking the material,and taking blood lipids by means of cardiac blood sampling:Triglyceride(TG),Total cholesterol(TC),High density lipoprotein(HDL),Low density lipoprotein(LDL).The intima thickness,media thickness and intima-media thickness ratio of rat cervical artery were measured by HE staining.Western-blot method was used to detect the expression of related factor proteins:Ghrelin,ABCG1,Toll-like receptor 4(TLR4),peroxisome proliferator-activated receptor gamma(PPARγ),and liver X receptor(LXRα).RESULTSThe results of HE staining in each group:Compared with group A,the ratio of carotid intima and intima-media thickness in group B and C was significantly increased(P<0.05).Compared with group B,carotid intima and intima of group C were compared with group B.The thickness ratio was significantly increased(P<0.01).Compared with group C,the ratio of carotid intima and intima-media thickness in group D and E was significantly lower(P<0.01).Compared with group D,carotid intima of group E,There was no significant difference in the thickness of the intimamedia thickness,which was not statistically significant(P>0.05).Body weight of each group:Compared with group A,body weight of group B was significantly increased(P<0.01);compared with group B,body weight of group C,group D and group E was significantly lower(P<0.01);compared with group C,D,There was no significant difference in body weight between the E group(P>0.05).There was no significant difference in body weight between the E group and the D group(P>0.05).Blood glucose levels in each group:Compared with group A,there was no significant difference in blood glucose between group B(P>0.05),and blood glucose in group C was significantly higher(P<0.01).Compared with group B,blood glucose in group C was significantly higher(P<0.01);Compared with group C,blood glucose in group D was significantly lower(P<0.01).There was no significant difference in blood glucose between group E(P>0.05).There was no significant difference in blood glucose between group E and group D(P<0.05).Compared with group A,serum TC,TG and LDL were significantly increased in group B and C,and HDL was significantly decreased(P<0.05).Compared with group B,serum TC,TG and LDL were significantly increased in group C.HDL was significantly lower(P<0.01).Compared with group C,serum TC,TG and LDL were significantly increased in group D,HDL was significantly decreased(P<0.05),serum TC,TG and LDL were significantly increased in group E,and HDL was significantly decreased.(P<0.05);Compared with group D,there was no significant difference in blood lipids between group E,and there was no statistical significance(P>0.05).The expressions of Ghrelin,TLR4,PPARy,LXRa and ABCG1 in carotid intima of each group were compared.Compared with group A,the expression of PPARlγ,ABCG1 and Ghrelin protein in group B was significantly decreased(P<0.05),and there was no significant difference in TLR4 and LXRa protein expression.There was no statistical significance(P>0.05).The expression of TLR4 protein in group C was significantly increased,and the expression ofPPARy,LXRa ABCG1 and Ghrelin protein was significantly decreased(P<0.01).Compared with group B,the expression of TLR4 in group C was significantly increased.The expressions of PPARy,LXRa,ABCG1 and Ghrelin protein were significantly decreased(P<0.05).Compared with group C,the expression of TLR4 in group D was significantly decreased,and the expression of PPARy,LXRa,ABCG1 and Ghrelin protein was significantly increased(P<0.05).The expression of TLR4 protein was significantly decreased,and the expression of PPARy,LXRa and ABCG1 protein was significantly increased(P<0.05).There was no significant difference in the expression of Ghrelin protein(P>0.05).Compared with group D,the expression of Ghrelin protein in group E was significantly decreased(P<0.01),and there was no significant difference in the expression of TLR4,PPARy,LXRa and ABCG1 protein(P>0.05).CONCLUSION1.Successfully manufactured AS model by balloon injury with intimal combined with high-fat feeding method,and successful use of streptozotocin to produce diabetes(DM)model.Compared with group A,carotid intima-media thickness ratio increased,blood lipid increased,ABCG1 protein expression was significantly decreased in group B and C,and group C was more obvious,suggesting that abnormal glucose and l ipid metabolism can promote AS formation and hyperglycemia.Or DM can accelerate or promote the AS process through dyslipidemia and ABCG1 pathway,providing a new direction for AS prevention.Correlation analysis confirmed that Ghrelin has a negative correlation with TLR4,which may be upstream of TLR4;and ABCG1 is an important factor in cholesterol efflux,which is negatively correlated with blood lipid(LDL),suggesting that high fat and/or high glucose may be the Ghrelin/TLR4/PPARγ/LXRα/ABCG1 pathway aggravates lipid deposition and accelerates AS progression.2.The expression of Ghrelin in the arterial intima of rats in the high-fat and high-glycemic group was significantly decreased.The exogenous administration of Ghrelin improved the AS process in rats with abnormal glucose and lipid metabolism,suggesting that Ghrelin is involved in the occurrence and development of AS and glucose and lipid metabolism.Abnormal rat vascular endothelium has a protective effect.3.Compared with the rosuvastatin group,there was no significant difference in blood lipid,endometrial,intima-media thickness and expression of arterial intimal factors in the Ghrelin group,but blood glucose decreased significantly,indicating classic anti-AS,lipid-lowering,Compared with anti-inflammatory drugs,Ghrelin is at least not inferior to rosuvastatin,and has advantages in blood glucose regulation,providing a new intervention target for AS caused by DM. |
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