藁本内酯衍生物调控PI3K/AKT/NF-cB信号通路对激素性股骨头缺血性坏死的作用机制  

Mechanism of ligustilide derivatives on PI3K/AKT/NF-cB signaling pathway in steroid-induced avascular necrosis of femoral head

作　　者：刘建军 陈一新 张晓刚 齐鑫 陈欣 王多贤 马姣姣 胡紫阳 齐伟 LIU Jianjun;CHEN Yixin;ZHANG Xiaogang;QI Xin;CHEN Xin;WANG Duoxian;MA Jiaojiao;HU Ziyang;QI Weil(Sports Medicine Department,Affiliated Hospital of Gansu University of Chinese Medicine,Lanzhou 73000,China;Lanzhou First Peoples Hospital,Lanzhou 730000,China;Clinical College of Traditional Chinese Medicine,Gansu University of Chinese Medicine,Lanzhou 730000,China)

机构地区：[1]甘肃中医药大学附属医院运动医学科,兰州730000 [2]兰州市第一人民医院,兰州730000 [3]甘肃中医药大学中医临床学院,兰州730000

出　　处：《中华中医药杂志》2025年第3期1397-1402,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：兰州市城关区科技计划项目(No.001042001);张晓刚全国名老中医药专家传承工作室建设项目(No.国中医药人教函【2022】75号);2022年甘肃省中医药科研项目(No.GZKZ-2022-4);2022年甘肃省科技厅省级科技计划(No.22JR11RA126)。

摘　　要：目的:探讨藁本内酯衍生物(LIGc)通过调控PI3K/AKT/NF-kB信号通路抑制激素诱导的大鼠股骨头缺血性坏死的作用机制。方法:将72只SD大鼠随机分为2组:空白组12只、造模组60只,造模组第1天静脉注射1次脂多糖(4mg/kg),从第2天开始连续3d肌肉注射甲基强的松龙(40mg/kg,每天1次);空白组肌肉注射等量0.9%氯化钠溶液,8周后随机处死各组大鼠2只,取双侧股骨头进行模型验证。造模成功后随机分为模型组,阳性组,低、中、高剂量组,每组12只。造模成功后各组大鼠连续灌胃6周,采用Micro-CT、HE观察股骨头坏死、空骨陷窝;Western Blot检测大鼠股骨头组织中Bcl-2、Bax、Caspase-3、AKT、NF-xB等蛋白表达,qRT-PCR检测大鼠股骨头Bcl-2、Bax、Caspase-3基因表达。结果:与空白组比较,模型组大鼠股骨头骨小梁稀疏、断裂,软骨下囊性变形成,股骨头塌陷;Bax、Caspase-3、AKT、PCE2、COX2、NO、iNOS表达显著升高(P<0.01),Bcl-2蛋白表达显著降低(P<0.01);与模型组比较,LIGc各剂量组大鼠股骨头骨小梁稀疏、囊性变区域减少,LIGc中剂量组效果最好。此外,ICA增强了Bcl-2的表达,但减少了Bax的表达。与模型组比较,经LIGc干预后Caspase-3、AKT、PGE2、COX2、NO、iNOS表达显著升高(P<0.01)。结论:对于大鼠激素性股骨头缺血性坏死,LIGc可通过发挥其抗炎和抗凋亡特性起到一定的预防和治疗作用,有望发展其成为保护激素性股骨头缺血性坏死的临床药物。Objective:To investigate the anti-inflammatory and anti-apoptotic effects of ligustilide derivatives(LIGc)on steroid-induced avascular necrosis of femoral head in rats.Methods:Seventy-two SD rats were randomly divided into two groups:the blank group(n=12)and the model group(n=60).On the first day,the model group was intravenously injected with lipopolysaccharide(4 mg/kg)once.From the second day,they were intramuscularly injected with methylprednisolone(40 mg/kg,once a day)for three days.The blank group was intramuscularly injected with the same volume of 0.9%sodium chloride solution.After 8 weeks,2 rats from each group were randomly sacrificed,and the bilateral femoral heads were taken for model verification.After successful modeling,the model group was randomly divided into the model group,the positive group,and the low-,medium-,and high-dose groups,with 12 rats in each group.After successful modeling,the rats in each group were continuously gavaged for 6 weeks,Micro-CT and HE were used to observe femoral head necrosis and hollow bone lacunae.Western Blot was used to detect the expressions of Bcl-2,Bax,Caspase-3,AKT,NF-kB in the femoral head tissue of rats,and qRT-PCR was used to detect the expressions of Bcl-2,Bax,Caspase-3 genes in the femoral head of rats.Results:Compared with the blank group,the trabeculae of the femoral head in the model group were sparse,fractured,subchondral cystic metasemesis and femoral head collapse.The expressions of Bax,Caspase-3,AKT,PGE,and COX2 were significantly decreased(P<0.01),while the expressions of NO and INOS were significantly increased.Compared with the model group,the trabecular bone of the femoral head of rats in LIGc dose groups was sparse and the cystic lesion area was reduced,and the medium-dose LIGc group had the best effect.In addition,ICA enhanced the expression of Bcl-2 but reduced the expression of Bax.The expressions of Caspase-3,AKT,PGE2 and COX2 were significantly decreased(P<0.01).Conclusion:In the treatment of steroid-induced avascular necrosis of femoral h

关 键 词：藁本内酯衍生物 激素性股骨头缺血性坏死 炎症 凋亡 

分 类 号：R285.5[医药卫生—中药学]