Effect Of Exogenous Apelin-13on The Formation Of Atherosclerosis In Rats

Objective: To study the effects of exogenous apelin-13peptide on theformation of atherosclerosis in rats,and to explore its possible mechanisms.Methods:60SD rats(7-8months old,170-220g)were randomlydivided into four groups: normal control group (group N), model group(group M),low-dose apelin group (group LA),high-dose apelin group(group HA),15rats in each group. N group were fed with normal diet;M,LA and HA group were fed with high fat diet,Every two days givingdifferent dose of apelin-13through caudal vein when LA and HA groupswere fed with high fat diet,M group received saline intravenously in thesame way.In the beginning of high-fat feeding,giving rats of M, LA and HAgroups vitaminD3(60×104IU/kg)through intraperitoneal injection once.Atthe ending of the12th week,the animals were anesthetized for taking bloodsamples and ultrasonic testing.Then the animals were sacrificed andspecimens were taken.The kits checked serum lipids, malondialdehyde(MDA) and superoxide dismutase (SOD) levels of rats in each group.HEstaining observed the morphological changes of arterytissue,immunohistochemical dyeing observed vascular smooth muscle actin (α-SMA) and p22phox expression in each group,Ultrasound observedabdominal aortic lesions;Western blot detected the expression of p22phox，NF-kBp65,JNK and P-JNK.Results:1.Compared with N group，the lipids of the other three groupswere significantly increased except HDL-C (P <0.01)；the lipids showedno difference in M group,LA group and HA group（P＞0.05）.The MDA inLA group and HA group were significantly lower than that in Mgroup.Otherwise，the SOD has opposite conclusion (P <0.01).2.HE stainingof the aortic arch:In N group the aortic morphology was normal,there wereno pathological changes.M group and LA group had obvious signs ofatherosclerosis.In HA group，there were a little less smooth intima withslightly thickened,and smooth muscle cells arranged in disorder, with asmall amount of fibrosis and inflammatory cells infiltrating.3.Ultrasonicdetection of abdominal aorta:N group and HA group showed no significantlesions.Abdominal aorta intima of M and LA group was lessclear,roughs,discontinuous and thickened.Even it showed small proliferousplaques in the lumen.4Immunohistochemical dyeing showed that theexpression of α-SMA in M group，LA group and HA group aorta weresignificantly lower than that in N group (P<0.01);α-SMA expression of HAgroup and LA group was significantly higher than that in Mgroup(P<0.01);It was also different between LA and M group.(P<0.01).The expression of p22phox in LA and HA group show significant difference with M group(P<0.01)，it also showed significant differencebetween LA group and H group(P <0.01).5. p22phox, NF-kBp65andp-JNK in M group，LA group and HA group were significantly higher thanthose in N group (P<0.01);Compared with LA group and HA group，expression of p22phox,NF-kBp65of M group were significantly higher（P<0.01);P-JNK expression was no significant difference between LAgroup and M group(P>0.05)；Expression of NF-kBp65，p22phox andp-JNK in HA group was lower than that in LA group(P<0.01);JNKexpression of each group showed no significant difference (P>0.05).Conclusion: Exogenous apelin-13peptide can reduce the effects onoxidative stress in atherosclerotic rats,it can inhibit smooth muscle cellproliferating，the mechanisms may be preventing JNK/NF-kB signalingpathway activating.