自噬对高胆固醇饮食大鼠下颌骨结构改变的影响研究

Jaw bone microstructural defect induced by high cholesterol diet in rats by regulating autophagy

目的探讨自噬对高胆固醇饮食大鼠下颌骨结构改变的影响及辛伐他汀的治疗效果。方法将30只SD大鼠随机分为正常饮食组(NC组)10只、高胆固醇组20只;喂养24周后,高胆固醇组再随机分成两组,每组10只,一组继续喂养高胆固醇饲料(HC组),另一组在高胆固醇饲料中加入5 mg/kg辛伐他汀(HC+SIM组)。喂养32周后,取大鼠空腹血进行生化检测;处死大鼠后对下颌骨进行骨组织形态分析;实时荧光定量PCR(qRT-PCR)及免疫组织化学染色检测各组自噬相关基因Lc3及p62的mRNA和蛋白表达水平。结果 (1)3组总胆固醇和低密度脂蛋白水平总的比较,差异均有统计学意义(F值分别为21.539、16.596,均P <0.05);其中NC组和HC+SIM组总胆固醇和低密度脂蛋白水平均低于HC组(均P <0.05),而NC组和HC+SIM组组间比较,差异无统计学意义(P>0.05)。(2)与NC组比较,HC组大鼠骨体积分数、骨小梁厚度、骨小梁数目明显下降,而骨小梁间隔增加,Lc3及p62 mRNA表达水平明显升高,差异均有统计学意义(均P <0.05);与HC组比较,HC+SIM组骨体积分数、骨小梁厚度、骨小梁数目均明显升高,骨小梁间隔减小,p62 m RNA和蛋白表达水平明显下降,差异均有统计学意义(均P <0.05);而NC组和HC+SIM组这些指标组间比较,差异均无统计学意义(均P> 0.05)。结论自噬可能参与调控高胆固醇饮食大鼠下颌骨结构的改变,辛伐他汀能够改善高胆固醇饮食导致的大鼠下颌骨微结构的破坏。

Objective To investigate the role of autophagy on the change of mandibular microstructure and the therapeutic effect of simvastatin in rats on high cholesterol diet. Methods A total of thirty SD rats were divided into three groups,normal diet group(NC),high cholesterol diet group(HC),simvastatin + high cholesterol diet group(HC+SIM).After feeding 32 week,venous blood of fasting for 12 hours was collected to assay triglyceride,cholesterol,high-density lipoprotein and low density lipoprotein. The static histomorphometric changes in the jaw bone tissues in individual rats was evaluated after puting the rat to death. The expression LC3 an p62 gene mRNA and protein were detected by the real-time fluorescence quantitative PCR and immunohistochemistry. Results(1)There were significant differences in total cholesterol and low density lipoprotein levels among the three groups(F = 21.539,16.596,P < 0.05);the levels of TC and LDL in NC group and HC+SIM group were lower than those in HC group(P < 0.05),but there was no significant difference between NC group and HC+SIM group(P > 0.05).(2)Compared with NC group,the trabecular bone volume,tra-becular thickness and trabecular number of HC group were significantly decreased,while trabecular seperation was increased,and the m RNA expression levels of Lc3 and p62 were significantly increased(P < 0.05). Compared with HC group,the trabecular bone volume,trabecular thickness,number oftrabecular bone in HC+SIM group were significantly increased,trabecular seperation was decreased,and p62 m RNA and protein expression levels were significantly decreased(P < 0.05),while there was no significant difference between NC group and HC+SIM group(P > 0.05). Conclusion Autophagy may be involved in regulating the changes in the microstructures of the jaw bone in hyperlipidemia rats and simvastatin can improve the jaw bone microstructure.