有氧运动降低动脉粥样硬化大鼠血清和组织Lp-PLA2水平及意义

Inhibition of Lp-PLA2 in the Serum and Tissues of Atherosclerotic Rats through Aerobic Exercise and its Significance

目的:脂蛋白相关磷脂酶A2(Lp-PLA2)是一种促动脉粥样硬化(AS)的促炎因子,血清Lp-PLA2的减少可能与运动减轻肥胖的糖脂代谢紊乱有关。但鲜有运动对AS的组织Lp-PLA2水平的影响及意义的研究报道。通过研究4周有氧运动对AS造模大鼠血清和组织(肝、腓肠肌和脂肪)Lp-PLA2水平的影响,探讨Lp-PLA2在运动减轻AS严重程度和糖脂代谢紊乱中的作用。方法:采用腹腔注射维生素D3联合8周高脂饲料喂养的方法建立AS模型大鼠。将建模成功的16只雄性AS大鼠随机分为AS安静组(n=8)和AS运动组(n=8),AS运动组进行4周递增负荷的中等强度有氧运动。同周龄、喂普通饲料的雄性大鼠作为正常对照组(Con组,n=8)。4周运动前、后检测FBG和血脂4项;ELISA检测空腹血清胰岛素(FINS)和血清Lp-PLA2的水平。4周运动后,采用油红O染色和HE染色分别检测主动脉的AS斑块数量、AS程度;免疫组化检测巨噬细胞浸润(CD68),Western blot检测肝、腓肠肌和脂肪组织的Lp-PLA2蛋白水平。结果:1)伴随着脂代谢紊乱(血脂四项异常)、主动脉出现AS改变(大体标本的AS斑块和显微镜下的AS病理变化)和巨噬细胞浸润增加,AS大鼠的血清、肝、腓肠肌和脂肪组织的Lp-PLA2水平比Con组大鼠显著增加;2) 4周有氧运动显著降低了AS大鼠的血清和组织(肝、腓肠肌和脂肪)LpPLA2水平,与此同时,改善了脂代谢紊乱、减少了主动脉的AS斑块数量、减轻主动脉的AS病理改变和巨噬细胞浸润。结论:4周有氧运动减轻AS大鼠的主动脉AS程度和减轻脂代谢紊乱,该作用可能与运动降低AS大鼠血清和肝、腓肠肌、脂肪等组织的Lp-PLA2蛋白水平有关,且减少的Lp-PLA2很可能是通过减轻巨噬细胞浸润来减轻主动脉AS程度。

Object:Lipoprotein-associated phospholipase A2(Lp-PLA2)has become a focus in recent years due to its specific pro-inflammatory effect in atherosclerosis(AS).Some research reports suggest that the decrease of serum Lp-PLA2 might be associated with the improvement of dyslipidemia through aerobic exercise in obesity.Until now,there is still no report about exercise-induced changes of Lp-PLA2 in tissues of AS.So in this study the levels of Lp-PLA2 were detected in multiple tissues(including liver,gastrocnemius and adipose tissue)of AS model rats after 4-week aerobic exercise for exploring the role of Lp-PLA2 in exercise-induced alleviation of AS and improvement of glycolipid metabolism as well as its significance.Method:AS modelrats were established byintraperitoneal injection of Vitamin D3 in combination with 8-week high fat diet feeding.For verifying the successful establishment of AS rats,one rat from Con group and two rats from AS model group were taken randomly to determine the levels of blood glucose and lipid as well as morphological and pathological alterations of the aorta.Then,16 successfully established AS rats were randomly divided into AS group(n=8)and exercised AS group(EAS,n=8).EAS group rats did 4-week moderate intensity aerobic exercise on treadmill with gradually increasing intensity while Con and AS rats kept sedentary life,with allof the rats were fed with common diet during the experiments.Before and after 4-week exercise,the blood of the three group rats were drawn to measure the circulating levels of fasting blood glucose(FBG),triglyceride(TC),total cholesterol(TG),LDLand HDL.The fasting insulin(FINS)and serum Lp-PLA2 were measured by ELISA.The rats were anaesthetized and sacrificed after 4-week exercise,and the liver,gastrocnemius and perirenal fat of the rats were collected to detect the protein levels of Lp-PLA2(Western blot),and the full-length aorta of the rats were separated to determine AS arteriosclerosis plaque(oil red O staining and histopathological examination)and macrophages infiltration(immunohistochemistry).Results:1)Compared with the Con rats,the levels of serum Lp-PLA2 and the protein levels of Lp-PLA2 in the livers,gastrocnemius and adipose tissues of AS rats were significant increased,accompanied with the disorders of glucose and lipid metabolism(increases of TC,TG,LDL and FINS as well as decrease of HDL,but unchanged FBG),appearances of atherosclerotic plaques and atherosclerotic pathological characteristic in aorta as well as enhancement of macrophage infiltration in aorta(reflected by increase of macrophage-specific marker CD68).2)The levels of serum Lp-PLA2 and protein levels of Lp-PLA2 in the livers,gastrocnemius and adipose tissues of AS rats were significantly decreased by 4-week aerobic exercise,accompanied withthe improvement of glucose and lipid metabolism,alleviation of atherosclerotic plaques and atherosclerotic pathological characteristic in aorta as well as reduction of macrophage infiltration in aorta.Conclusions:These results suggested that the beneficial effects of exercise on reducing the severity of AS in aorta and improving the disorder of glucose and lipid metabolism in AS rats might be related to the decrease of Lp-PLA2 in serumand multiply tissues(livers,gastrocnemius and adipose tissues)of AS rats.Furthermore,the reduced Lp-PLA2 was likely to alleviate the severity of aortic atherosclerosis by reducing macrophage infiltration.