青蒿琥酯对大鼠胶原诱导性关节炎骨质疏松的保护作用

摘要

目的：探讨青蒿琥酯是否能抑制CIA大鼠骨质破坏及预防骨质疏松及其可能的机制。方法随机将大鼠分为对照组、CIA模型对照组、MTX组、青蒿琥酯组、甲基泼尼松龙组及rhTNFR：Fc组并灌胃给药。行大鼠四肢关节钼靶拍片，并予影像学评分。收取大鼠血液和尿液测定血钙、血磷、尿钙、尿磷的含量，同时测定血、尿液中脱氧吡啶啉（ DPD）含量、血清碱性磷酸酶、骨保护钙素含量，并采用骨密度仪对大鼠全身骨骼进行扫描。结果青蒿琥酯组与MP、MTX和CIA比较有统计学意义（P＜0.01），21w时与10w比较无统计学意义。 rhTNFR：Fc组在与健康组比较均无统计学意义，与其他药物干预组比较均有统计学意义（P＜0.05）；CIA模型对照组、甲氨蝶呤组、甲基泼尼松龙组各项检测指标与造模后21w与10w比较有统计学意义（ P ＜0.01）。骨密度检测提示甲基泼尼松龙及甲氨蝶呤组在第10w及21w均不能抑制骨质疏松的发生，而青蒿琥酯组和rhTNFR：Fc组于第10w及21w均可预防骨质疏松的发生。影像学亦显示青蒿琥酯组和rhTNFR：Fc组可预防CIA大鼠发生骨质疏松。结论青蒿琥酯有预防CIA大鼠骨质疏松及抑制骨质破坏的作用，其可能的机制是抑制TNF-α的分泌、作用于OPG/RANK/RANKL信号系统从而阻断破骨细胞的生成和活化。%Objective To investigate whether artesunate can inhibit bone destruction and prevent osteoporosis in collagen-induced arthritis ( CIA) rats and its possible mechanism.Methods The rats were randomly divided into blank control group, CIA model control group, MTX group, artesunate group, methyl prednisolone group ( MP ) , and rhTNFR:Fc group.Drugs were given intragastrically in each group.Molybdenum target radiography was performed in rat limb joints and scored.Blood and urine samples were collected for the test of calcium, phosphorus content.Meanwhile, the content of deoxypyridinoline ( DPD), alkaline phosphatase (ALP), osteoprotegerin ( OPG) in blood and urine was examined.Total bone of the rats was scanned using bone densitometry.Results Comparison among artesunate group, methyl prednisolone group, MTX group, and CIA group was of statistical significance ( P<0.01 ) .Comparison between data of 21 weeks and data of 10 weeks was not statistical significance. Comparison of data between those in rhTNFR:Fc group and in healthy group was not statistical significance, but was statistically significant comparing with other drug intervention groups.All testing data between 21 weeks and 10 weeks in CIA model control group, MTX group, and MP group were statistically significant (P<0.01).The measurement of bone mineral density suggested that MP and MTX did not inhibit the occurrence of osteoporosis in 10 and 21 weeks, while artesunate and rhTNFR:Fc prevented the occurrence of osteoporosis in 10 and 21 weeks.Radiographic data also showed that artesunate and rhTNFR:Fc prevented CIA rats from the occurrence of osteoporosis.Conclusion Artesunate significantly inhibit bone destruction and prevent CIA rats from osteoporosis, with the possible mechanism of inhibition of TNF-αsecretion and the influence in OPG/RANK/RANKL signaling system thereby blocking the formation and activation of osteoclasts.