羟基红花黄色素A联合扁桃苷对激素性股骨头坏死大鼠的作用研究  

Pharmacological Effects of Hydroxysafflor Yellow A Combined with Amygdalin on Steroid-induced Avascular Necrosis of Femoral Head in Rats

作　　者：曾晓会 卓俊城 杨帆[3,4] 谢凯枫 甘海宁 黄雪君 陈玉兴 ZENG Xiaohui;ZHUO Juncheng;YANG Fan;XIE Kaifeng;GAN Haining;HUANG Xuejun;CHEN Yuxing(Guangdong Institute of Traditional Chinese Medicine Engineering,Guangzhou 510095 Guangdong,China;Guangdong Key Laboratory of Traditional Chinese Medicine Research and Development,Guangzhou 510095 Guangdong,China;Guangzhou University of Traditional Chinese Medicine,Guangzhou 510405 Guangdong,China;First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine,Guangzhou 510405 Guangdong,China)

机构地区：[1]广东省中医药工程技术研究院,广东广州510095 [2]广东省中医药研究开发重点实验室,广东广州510095 [3]广州中医药大学,广东广州510405 [4]广州中医药大学第一附属医院,广东广州510405

出　　处：《中药新药与临床药理》2019年第11期1284-1290,共7页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家自然科学基金面上项目（81473697）

摘　　要：目的研究羟基红花黄色素A(Hydroxysafflor yellow A,HSA)和扁桃苷(Amygdalin,AG)联合用药(HSAAG)对激素性股骨头坏死(SANFH)大鼠的作用机制。方法将雄性SD大鼠随机分为正常组、模型组、HSAAG-H组(高剂量组,HSA 12 mg·kg^-1+AG 18 mg·kg^-1)和HSA-AG-L组(低剂量组,HSA 6 mg·kg^-1+AG 9 mg·kg^-1),每组20只。采用腹腔注射(24 h注射1次,共2次)脂多糖(LPS,300μg·kg^-1)+肌肉注射(24 h注射1次,共3次)甲强龙(65 mg·kg^-1)和青霉素G(1×105 U)的方法制备SANFH大鼠模型。造模1周后开始腹腔注射给药,2 d给药1次。于造模后的第8周和第12周,分别从每组随机抽取10只大鼠,取材并进行血液流变学检测;采用CT扫描观察大鼠股骨头微观结构;HE染色观察大鼠股骨头组织病理学变化;Western Blot法检测股骨头中PI3K、AKT、BCL2和BAX蛋白表达情况。结果在实验第8周时,与正常组比较,模型组的全血黏度(低切、中切、高切)及血浆黏度均明显升高(P<0.05,P<0.01);CT扫描及HE染色均显示股骨头出现了明显的坏死现象;大鼠股骨头的PI3K和BCL2蛋白表达明显下调(P<0.05),BAX蛋白表达明显上调(P<0.01),AKT蛋白表达无明显变化(P>0.05)。与模型组比较,HSA-AG高、低剂量组的全血黏度(低切、中切、高切)及血浆黏度均明显降低(P<0.01),股骨头结构及其病理损伤均有一定程度的改善,PI3K及BCL2蛋白表达水平明显上调(P<0.05,P<0.01),BAX蛋白表达水平明显下调(P<0.01);HSA-AG高剂量组的AKT蛋白表达水平明显上调(P<0.01)。在实验第12周时,与正常组比较,模型组的血液流变学指标、股骨头微观结构及病理学观察,以及PI3K/AKT/BCL2/BAX通路相关蛋白表达均无明显变化(P>0.05),呈现一定的自愈倾向。与模型组比较,HSA-AG高剂量组的全血黏度(低切、中切、高切)及血浆黏度均明显降低(P<0.01),而股骨头微观结构、病理学观察,以及PI3K/AKT/BCL2/BAX通路相关蛋白表达均无明显变化(P>0.05)。结论HSA-AGObjective To study the mechanism of the combining application of hydroxysafflor yellow A(HSA)and amygdalin(AG)on steroid-induced femoral head avasculan necrosis in rats.Methods Rats were randomly divided into normal group,model group,high-dose HSA-AG group(HSA-AG-H,HSA 12 mg·kg^-1+AG 18 mg·kg^-1)and low-dose HSA-AG group(HSA-AG-L,HSA 6 mg·kg^-1+AG 9 mg·kg^-1).Except the normal group,LPS 300μg·kg^-1 was injected intraperitoneally twice every 24 hours,followed by intramuscular injection of methylprednisolone 65 mg·kg^-1 and penicillin 1×105 U,three times every 24 hours.After one week,the rats were intraperitoneally injected with HSA-AG once every two days.At the 8th and 12th weeks,10 rats from each group were picked randomly to observed the hemorheological indexes,and CT scanning was used to observe the microstructure of the femoral head of rats;HE staining was used to observe the histopathological changes of the femoral head of rats.Proteins in apoptotic signal pathway were detected by Western Blot,to judge the degree of necrosis,including PI3K,AKT,BCL2 and BAX.Results At the 8th week of the experiment,compared with the normal group,the whole blood viscosity(low,middle and high shear)and plasma viscosity of the model group rats were significantly increased(P<0.05,P<0.01);CT scan and HE staining showed that the femoral head had obvious necrosis,and the expression of PI3K and BCL2 protein in the femoral head of rats were significantly decreased(P<0.05,P<0.01).Protein expression of BAX was increased obviously(P<0.01),and no significant change of AKT protein expression(P>0.05).Compared with the model group,the whole blood viscosity(low,middle and high shear)and plasma viscosity of the HSA-AG-H and HSA-AG-L group were significantly lower(P<0.01);the structure of femoral head and pathological damage of the HSA-AG group were improved to some extent;the expression of PI3K and BCL2 protein in the HSA-AG-H and HSA-AG-L groups were significantly higher(P<0.05,P<0.01).The level of BAX protein expression was significan

关 键 词：激素性股骨头坏死 羟基红花黄色素A 扁桃苷 血液流变学 凋亡信号通路 

分 类 号：R285.5[医药卫生—中药学]