运动对自发性高血压大鼠主动脉平滑肌内质网应激及胶原含量的影响

摘要

This paper observes the effect of exercise training on endoplasmic reticulum stress and collagen content in thoracic aorta in spontaneous hypertensive rats and investigates the effect of exercise on the relation between ERS and remodeling.Methods： SHRs 80 subjects were assigned randomly to two groups,IE group trained in interval training,and CR group was set as control group.Blood pressure and blood lipid were measured every four weeks.These rats were sacrificed randomly at the start of this study,4th,8th,12th and 16th week,6 rats in each group each time.The aorta was collected and dyed with Masson to observe the pathological change of thoracic aorta under microscope;micro holography system was used to calculate collagen volumetric fraction（CVF） of the aorta.The expressions of glucose-regulated protein 78（GRP78） and caspase-12 in the aortic smooth muscle cells,TGFβ1 in SHR thoracic aorta were measured by immunohistochemistry.Results：（1） CVF in thoracic aorta increased significantly in CR group compared with that in IE group at 12th and16th week（P0.05）.（2） Compared with that in CR group,the expression of TGFβ1 in IE group decreased at 4th,8th and12th week（P0.05）.（3） while the blood pressure and the expressions of GRP78 and caspase-12 in the aortic smooth muscle cells decreased in the rats of IE group compared with CR group significantly,respectively.Conclusion： Long term exercise training might inhibit the activation of ERS in the aortic smooth muscle cells of hypertensive rats.Long term interval exercise training can decrease collagen content in thoracic aorta of SHR.Local TGFβ1 decrease induced by interval exercise training in SHR is probably involved in the development of collagen decrease.%目的：观察运动对自发性高血压大鼠（SHR）胸主动脉胶原含量及TGFβ1表达的影响及平滑肌细胞内质网应激（ERS）的调节作用,探讨运动对ERS与血管重构关系的作用.方法：80只自发性高血压大鼠随机分为运动组和对照组,运动组进行连续16周的运动.每隔4周监测血压.分别于实验第0、4、8、12、16周时随机分批处死SHR（每次每组6只）,取胸主动脉行Masson染色,观察病理变化并计算主动脉胶原容积分数（CVF）,免疫组化法测定SHR胸主动脉管壁转化生长因子β1（TGFβ1）、主动脉平滑肌细胞GRP78和caspase-12的蛋白表达.结果：（1）实验第12、16周,对照组SHR主动脉CVF均较运动组高（P〈0.05）.（2）实验第4、8、12周时运动组SHR主动脉TGFβ1的表达均较对照组低（P〈0.05）.（3）SHR运动组大鼠主动脉平滑肌细胞GRP78和caspase-12蛋白表达较SHR对照组明显减弱.结论：运动可能抑制高血压大鼠主动脉血管平滑肌细胞内质网应激反应的激活,也可使SHR胸主动脉胶原含量的增龄性变化减缓,而局部TGFβ1含量降低可能是导致其胶原含量减少的重要机制之一.