淫羊藿苷介导PI3K/Akt信号通路干预大鼠早期激素性股骨头坏死的研究  

Effect of icariin mediated PI3K/Akt signaling pathway on early steroid-induced avascular necrosis of the femoral head in rats

作　　者：石威 金鑫 王金凤 王志洲 王杰[2] 侯燕 严伟 姜红江 SHI Wei;JIN Xin;WANG Jin-feng;WANG Zhi-zhou;WANG Jie;HOU Yan;YAN Wei;JIANG Hong-jiang(Shandong Province Wendeng Orthopaedic Hospital,Weihai 264400,China;Anhui University of Chinese Medicine,Hefei 230012,China)

机构地区：[1]山东省文登整骨医院,山东威海264400 [2]安徽中医药大学,安徽合肥230012

出　　处：《现代药物与临床》2022年第12期2680-2686,共7页Drugs & Clinic

基　　金：山东省威海市中医药科技项目(2021N-21)。

摘　　要：目的探讨淫羊藿苷调控磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(Akt)信号通路干预大鼠早期激素性股骨头坏死的作用机制。方法50只SD大鼠随机分为对照组、模型组和淫羊藿苷10、20、40 mg/kg组,每组10只。除对照组外,其余各组ip脂多糖和im甲泼尼龙制备激素性股骨头坏死大鼠模型。淫羊藿苷组大鼠分别ig 10、20、40 mg/kg的淫羊藿苷,对照组、模型组均ig等量生理盐水,每天1次,连续6周。采用Micro-CT评估造模是否成功并分析骨密度(BMD)、骨体积密度(BV/TV)、骨表面积密度(BS/TV)、骨小梁厚度(Tb.Th)、骨小梁数量(Tb.N)、骨小梁分离度(Tb.Sp);ELISA法检测血清中血管内皮生长因子(VEGF)、一氧化氮(NO)水平;Western blotting法检测股骨头PI3K、Akt、磷酸化Akt(pAkt)蛋白的表达。结果与对照组比较,模型组BMD、Tb.Th、BV/TV、Tb.N、BS/TV、VEGF和NO水平明显降低,Tb.Sp明显增高(P<0.05);与模型组比较,淫羊藿苷组的BMD、Tb.N、BV/TV、Tb.Th、BS/TV、VEGF和NO水平明显增高,Tb.Sp明显降低(P<0.05)。与对照组比较,模型组PI3K和p-Akt蛋白表达均减少(P<0.05);与模型组比较,淫羊藿苷组PI3K和p-Akt蛋白表达均增加(P<0.05)。结论淫羊藿苷能够有效缓解激素性股骨头坏死的进展,其机制可能与调节血清中VEGF、NO水平和增加骨组织中PI3K、Akt、p-Akt蛋白的表达有关,从而诱导血管修复与新生,促进骨形成和愈合。Objective To explore the mechanism of icariin PI3K/Akt signaling pathway in the intervention of early steroid-induced femur head necrosis in rats.Methods Fifty SD rats were randomly divided into control group,model group,icariin 10,20,40 mg/kg group,with 10 rats in each group.Except for the control group,the other groups were successively injected with lipopolysaccharide and methylprednisolone by intraperitoneal injection,to prepare the Hormonal necrosis of the femoral head model.Icariin group were given 10,20,and 40 mg/kg icariin intragastrically,respectively,while control group and model group were given the same amount of normal saline intragastrically,once daily,for 6 weeks.Micro-CT was used to evaluate the success of modeling and to analyze BMD,BV/TV,BS/TV,Tb.Th,Tb.N,and Tb.Sp.ELISA was used to detect the levels of VEGF and NO in serum.Western blotting was used to detect PI3K,Akt,p-Akt protein.Results Compared with the control group,the levels of BMD,Tb.Th,BV/TV,Tb.N,BS/TV,VEGF and NO were significantly decreased in model group,while the levels of Tb.Sp were significantly increased(P<0.05).Compared with model group,the levels of BMD,Tb.N,BV/TV,Tb.Th,BS/TV,VEGF and NO were significantly increased in icariin group,while the levels of Tb.Sp were significantly decreased(P<0.05).Compared with control group,PI3K and P-Akt protein expression in model group were decreased(P<0.05).Compared with model group,PI3K and P-Akt protein expression were increased in icariin group(P<0.05).Conclusion Icariin can effectively alleviate the progression of steroid-induced femoral head necrosis,and its mechanism may be related to regulating the levels of VEGF and NO in serum and increasing the expression of PI3K,Akt and p-Akt in bone tissue,thus inducing vascular repair and regeneration and promoting bone formation and healing.

关 键 词：淫羊藿苷 激素性股骨头坏死 磷脂酰肌醇3激酶/蛋白激酶B信号通路 骨密度 血管内皮生长因子 一氧化氮 

分 类 号：R285[医药卫生—中药学]