摘要
目的
动脉粥样硬化是一种慢性的动脉疾病,发病人群以老年人居多。动脉粥样硬化可导致冠心病、心绞痛、心肌梗死、脑血栓、脑出血、脑萎缩、痴呆等多种疾病,严重危害人类的健康。通络汤具有益气补肾、活血通络的功效,用于临床效果较好。为了进一步研究其对动脉硬化的早期防治作用,本实验观察了通络汤对动脉粥样硬化(As)大鼠的作用效果,并探讨其抗As的可能作用机制。
方法
SPF级纯种Wistar大鼠60只,雌雄各半,体重170±20g,随机分成6组,每组10只。即正常对照组、高脂饲料组、通心络胶囊组、通络汤低、中、高剂量组。在造模过程中即开始给药。通络汤浓缩液(由黄石市中医院提供,常规煎煮):高浓度2.7g/ml、中浓度1.35g/ml、低浓度0.675g/ml;通心络胶囊配置成混悬液,浓度为2.05%。上述各组均按1ml/100g体重的剂量于每日早8时灌胃,每日一次。连续给药10周后,禁食12小时,断头取血,检测大鼠血脂浓度、血清NO、血浆血栓素B_2(TXB_2)、6-Keto-PGF_(1α)水平,并取主动脉作病理学检查。
结果
1、一般指标的变化
正常组大鼠毛色光泽,活动自如,反应灵敏,饮食正常。高脂饲料组体重增长较快,皮下脂肪厚,但随实验进程,毛发色泽暗淡,活动减少,反应迟钝,精神状态较差,进食量减少。通心络胶囊组较对照组活动稍有减少、反应尚灵敏、皮毛光泽、进食量稍有减少。通络汤高、中剂量组活动稍有减少,反应灵敏,皮毛尚光泽,食欲稍有减退。通络汤低剂量组活动减少,反应欠灵敏,皮毛色泽暗淡,食欲减退。
2、TC、TG、LDL、HDL的变化
高脂饲料组TC、TG、LDL较正常对照组明显升高(p<0.01),HDL降低(p<0.01);通心络胶囊组及通络汤各剂量组总TC、TG、LDL较高脂饲料组显著降低(p<0.01),而HDL升高(p<0.01)。通络汤高剂量组与通心络胶囊组相比无差别。
3、血清NO的变化
高脂饲料组NO浓度较正常对照组显著降低(p<0.01)。通心络胶囊组、通络汤中、高剂量组NO显著升高(p<0.01)。通络汤中、高剂量组与通心络胶囊组相比无差别。
4、血浆6-Keto-PGF_1α和TXB_2的变化
高脂饲料组血浆6-Keto-PGF_1α水平较正常组显著降低,TCB_2、TXB_2/PGF_(1α)显著升高(p<0.01);通络汤各剂量组血浆6-Keto-PGF_(1α)水平较高脂组均显著升高(p<0.01),通心络胶囊组及通络汤各剂量组血浆TXB_2,TXB_2/PGF_1α的水平均显著降低(p<0.01);通络汤各剂量组血浆6-Keto-PGF_(1α)水平较通心络胶囊组均有显著差别,中、高剂量组血浆TXB_2水平无显著差别,各剂量组TXB_2/PGF_(1α)的水平无显著差别。
5、胸主动脉形态学改变
5.1肉眼观察:正常组血管弹性好,内膜表面平滑,富有光泽;高脂模型组动脉弹性减低,管壁增厚,内膜面光泽度稍差;通心络胶囊组及通络汤各治疗组与正常组相比变化不明显。5.2光镜观察:正常组动脉内膜光滑,EC排列整齐、无缺失,内膜下间隙较小;高脂模型组血管壁增厚,内膜不光滑,EC呈连续性缺失,底层胶原纤维暴露,大量MC粘附于内皮表面或潜入内皮下,内皮下间隙增宽;通络汤低剂量组组内膜较光滑,局部有少量MC粘附,可见EC缺失,但明显好于模型组;通心络胶囊组及通络汤中、高剂量组与正常组相比未见明显差别。
结论
本实验成功复制Wistar大鼠食饵性高脂血症及早期AS病变模型,通络汤用药后,观察大鼠血脂浓度、血清NO、血浆血栓素B_2(TXB_2)、6-Keto-PGF_(1α)水平及形态变化。结果表明:
1、通络汤可调节高脂血症大鼠的脂代谢紊乱,降低TC、TG、LDL,升高HDL;
2、通络汤可改善EC功能,增强NO活性;
3、通络汤能够显著降低高血脂大鼠血浆中血栓素A_2的量,升高PGI_2,降低TXA_2/PGI_2的比值,能明显改善两者平衡。
4、形态学观察发现(肉眼、光镜)能保护血管EC,通络汤减轻AS早期EC受损的程度。
Objective
Atherosclerosis is a chronic arterial disease,and the majority patients is the aged. Atherosclerosis is one of the most prevalent fatal diseases which can lead to various diseases such as coronary heart disease,angina pectoris,cardiac muscle infarction, cerebral embolism,cerebral hemorrhage,encephalanalosis,dementia.Tong luo soup was used in clinical and have got good effect which can supplement qi and tenify kidney,activate blood circulation and clear the channels.The present experiment is to study the effect of Tong luo soup on serum level and aortic morphology in early atherosclerosis rats fed by high fat diet and its possible mechanism.
Methods
Sixty Wister rats were randomly and equally divided into six groups:normal group,model group,Tongxinluo Capsules group,Tongluo low dose group,Tongluo middle dose group,Tongluo high dose group.Normal saline was given to rats of normal group and model group at the same volume and same way.The normal group was fed with standard chow,other groups were fed with high lipid diet.The serum levels of total cholesterol(TC),triglyceride(TG),low density lipoprotein(LDL),high density lipoprotein(HDL),nitric oxide(NO),6-Keto-PGF_1αand TXB2 were measured after eight weeks.Morphological changes of aorta were observed under gross and light microscopes.
Results
1.In model group,TC and TG and LDL were increased and HDL was decreased compared with normal group(P<0.01).After treating with Tongluo soup,TC and TG and LDL were decreased compared with model group(P<0.01),and HDL were increased compared with model group(P<0.01).
2.The content of NO was higher in model group compared with the normal group(p<0.01).The low dosage equisetum increased the bioactivity of NOS,decrease the release of NO.
3.In model group,the contents of 6-keto-prostacyclin lalpha(6-keto-PGF1α) was lower and thromboxane B2(TXB2)was higher compared with the normal group(p<0.01).After treating with Tongluo soup,6-keto-PGF_1αwas decreased compared with model group(P<0.01),and TXB_2 was increased compared with model group(P<0.01).
4.We found the changes of the early stage of atherosclerosis in model group:There were focal or transient areas of endothelium loss,monoeyte adhered to the subendothelial space or moved into the vascular wall,et al.Those changes of aorta endothelium in fed Tongluo soup animals were less compared with model group.
Conclusion
1.Tongluo soup has obvious effect on decreasing the serum levels of TC and TG and LDL,and increasing the serum level of HDL in atherosclerotie rats.
2.Tongluo soup can regulate the release of NO.
3.Tongluo soup can significantly reduce thromboxane A2 and increased PGI2.
4.Morphological changes of aorta were showed a significant effect of protecting aorta endothelial cell in rats fed with Tongluo soup.
引文
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