首页|银杏叶提取物基于TLR4/NF-κB通路对骨质疏松大鼠的干预效果及作用机制

银杏叶提取物基于TLR4/NF-κB通路对骨质疏松大鼠的干预效果及作用机制

Intervention effect and mechanism of ginkgo biloba extract based on TLR4/NF-B pathway in osteoporosis rats

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目的 分析银杏叶提取物基于TLR4/NF-κB通路对骨质疏松大鼠的干预效果及作用机制.方法 选取周龄在 4~6 周的SPF健康雌性SD大鼠 40 只,随机分对照组(A组)、骨质疏松组(B组)、阳性药物己烯雌酚组(C组)和银杏叶提取物(D组),适应性饲养 1 周后,第 2 周进行建模,饲养 3 个月后起给予药物干预,C组大鼠每日给予己烯雌酚 0.05 mg·kg-1·d-1,D组大鼠给予银杏叶提取物,以 200 mg·kg-1·d-1 的剂量给药,给药方式均采用灌胃给药.C组、D组进行药物干预 6 周,与此同时,A组、B组给予 10 mL·kg-1·d-10.9%氯化钠溶液灌胃.给药周期满6 周后,麻醉大鼠成功,处死大鼠,取出股骨组织,检测并观察各组大鼠碱性磷酸酶(alkaline phosphatase,ALP)、骨保护素(osteoprotegerin,OPG)、25-羟基维生素D3(25-hydroxyvitamin D3,25OHD)、抗酒石酸盐酸性磷酸酶(Tartrate-resistant acid phosphatase,TRACP)、钙离子(calcium ion,Ca2+)、镁离子(magnesian ion,Mg2+)、超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)、过氧化氢酶(catalase,CAT)水平及toll样受体4(toll-like receptor 4,TLR4)、核因子κB(nuclear factor kappa-B,NF-κB)蛋白表达.结果 与A组比较,B组、C组、D组ALP、TRACP、MDA、TLR4、NF-κB水平升高,OPG、25OHD、Ca2+、Mg2+、SOD、GSH-Px、CAT水平降低,差异有统计学意义(P<0.05);与B组比较,C组、D组ALP、TRACP、MDA、TLR4、NF-κB水平降低,OPG、25OHD、Ca2+、Mg2+、SOD、GSH-Px、CAT水平升高,差异有统计学意义(P<0.05);与C组比较,D组ALP、TRACP、MDA、TLR4、NF-κB水平降低,OPG、25OHD、Ca2+、Mg2+、SOD、GSH-Px、CAT水平升高,差异有统计学意义(P<0.05).结论 银杏叶提取可能会通过抑制TLR4/NF-κB通路活化来改善骨质疏松大鼠骨代谢水平及氧化应激反应,影响破骨细胞吸收,同时会调节机体Ca2+、Mg2+水平,未来对临床骨质疏松的治疗有重要意义.
Objective To investigate the intervention effect and mechanism of ginkgo biloba extract in osteoporosis rats based on toll-like receptor 4(TLR4)/nuclear factor-kappaB(NF-κB)pathway.Methods Forty healthy female Sprague-Dawley(SD)rats in the specific pathogen free(SPF)level aged 4-6 weeks were selected and randomly divided into control group(group A),osteoporosis group(group B),positive drug diethylstilbestrol group(group C)and ginkgo biloba extract(group D).After a week of adaptive feeding,modeling was conducted at the second week,and drug intervention was given starting from 3 months of feeding.Group C rats were given 0.05mg/kg of diethylstilbestrol daily,and group D rats were given ginkgo biloba extract at a dose of 200mg/kg per day,all administered by gavage.Group C and D received medication intervention for 6 weeks,while group A and group B received 0.9%sodium chloride solution 1mL/100g orally every day.After 6 weeks of administration,rats were anesthetized and femoral tissues were removed.Alkaline phosphatase(ALP),osteoprotectin(OPG),25-hydroxyvitamin D3(25OHD),tartrate resistant hydrochloric acid phosphatase(TRACP),calcium ions(Ca2+),Magnesium ion(Mg2+),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),catalase(CAT)levels,TLR4 and NF-κB protein expressions were detected.Results Compared to Group A,ALP,TRACP,malondialdehyde(MDA),TLR4,and NF-κB levels increased significantly in groups B,C and D,while the levels of OPG,25OHD,Ca2+,Mg2+,SOD,GSH-Px and CAT decreased obviously(P<0.05).Compared with Group B,levels of ALP,TRACP,MDA,TLR4,and NF-κB in group C and D were significantly reduced,while the levels of OPG,25OHD,Ca2+,Mg2+,SOD,GSH-Px and CAT were obviously elevated(P<0.05).Compared with Group C,the levels of ALP,TRACP,MDA,TLR4,and NF-κB decreased significantly in Group D,whereas the levels of OPG,25OHD,Ca2+,Mg2+,SOD,GSH-Px and CAT increased remarkably(P<0.05).Conclusion Ginkgo biloba extract may improve bone metabolism and oxidative stress response in osteoporosis rats by inhibiting the activation of the TLR4/NF-κB pathway,affect the absorption of osteoclasts and regulate the levels of Ca2+ and Mg2+ in the body,which is of great significance for the treatment of clinical osteoporosis in the future.

ginkgo biloba extractosteoporosis ratstoll-like receptor 4(TLR4)/nuclear factor-kappaB(NF-κB)pathwayoxidative stressbone metabolism

詹兴洪、章国荣、罗鸿波、柯学英、魏俊杰

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352000 福建省宁德市医院骨二科

银杏叶提取物 骨质疏松大鼠 TLR4/NF-κB通路 氧化应激 骨代谢

福建省中医药科研课题福建医科大学启航基金

2017FJZYLC3052017XQ1178

2024

河北医药
河北省医学情报研究所

河北医药

CSTPCD
影响因子:1.075
ISSN:1002-7386
年,卷(期):2024.46(2)
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