吡格列酮对去卵巢大鼠IL-1、IL-6、TNF-α水平的影响  

Effect of pioglitazone on IL-1β,IL-6,and TNF-α in ovariectomized rats

作　　者：孙晓婷[1] 吴迎爽 朱亦堃[1] 史书红[1] 李兴[1] 赵宝珍[1] 

机构地区：[1]山西医科大学第二医院,太原030001 [2]河北张家口市第一医院,河北张家口075000

出　　处：《中国骨质疏松杂志》2015年第2期152-157,共6页Chinese Journal of Osteoporosis

基　　金：山西省自然科学基金(2012011039-2)

摘　　要：目的本实验通过观察吡格列酮对去卵巢大鼠体重、血脂、FNS、HOMA-IR、E2、BMD、BALP及PPARγ2、IL-1β、IL-6、TNF-α的影响,探讨其与绝经后骨质疏松的关系及作用的可能机制。方法选用144只健康雌性3月龄Wistar大鼠作为研究对象,分为去卵巢组及假手术组,两组分别给予生理盐水、吡格列酮4 mg/(kg·d)或吡格列酮20 mg/(kg·d),在0、4、8、12 w不同时间点各取6只大鼠进行各项生化指标的测定,用DPX双能X线骨密度扫描仪检测实验动物骨量的变化,RT-PCR检测PPARγ2水平,酶联免疫吸附法测定IL-1β、IL-6、TNF-α、BALP水平。结果 1.去卵巢组大鼠与假手术组比较,体重、TG、CHO、LDL-C、FNS、HOMA-IR、PPARγ2、IL-1β、IL-6、TNF-α、BALP均升高,E2、HDL-C、BMD下降,差异有统计学意义(P<0.01)。2.去卵巢组大鼠以不同浓度吡格列酮干预后PPARγ2呈时间和剂量依赖性上升(P<0.05),IL-1β、IL-6、TNF-α及BALP水平呈时间和剂量依赖性下降(P<0.05),同时相关性分析结果证实PPARγ2与IL-1β、IL-6、TNF-α呈负相关(-0.5<r<0,P<0.05)。3.不同浓度吡格列酮干预后去卵巢组大鼠骨密度降低,差异有统计学意义(P<0.05)。结论 1.大鼠去卵巢后出现胰岛素抵抗,IL-1β、IL-6、TNF-α水平升高。2.吡格列酮激活PPARγ2转录活性上调其表达,在增加胰岛素敏感性、改善胰岛素抵抗的同时可能通过抑制破骨细胞刺激因子IL-1β、IL-6、TNF-a的水平,降低PMOP高转换率,但也使成骨细胞标志BALP水平下降,抑制成骨过程,总体上加重PMOP发生风险。Objective To explore possible mechanism of the effect of pioglitazone and the relation between pioglitazone and postmenopausal osteoporosis by observing the effect of pioglitazone on body weight,blood lipid,FNS,H0MA4 R,E2,BMD,BALP,PPARγ2,IL-1β,IL-6,and TNF-α in ovariectomized rats.Methods One hundred and forty-four 3-month-old healthy female Wistar rats were divided into Sham-ovariectomized group and ovariectomized group.Rats in two groups were given normal saline,pioglitazone 4 mg/kg·d or pioglitazone 20 mg/kg·d respectively.On 0,4,8,and 12 weeks 6 rats from each group were randomly selected to measure relevant biochemical indicators.Bone mass of the animals was detected using duel-energy X-ray absorptiometry.PPARγ2 was examined using RT-PCR.IL—1β,IL-6,TNF-α,and BALP were measured using ELISA method.Results 1） Body weight,TG,CHO,LDL-C,FNS,H0MA4 R,PPARγ2,IL-1β,IL- 6,TNF-α,and BALP increased,and E2,HDL-C,and BMD decreased in ovariectomized group,compared to another group.The difference was statistically significant（P〈0.01）.2） With different doses of pioglitazone treatment in ovariectomized group,H0MA4 R decreased dose-dependently { P〈0.01）,PPAR72 increased time-and dose-dependently（P〈0.05）,and IL-1β,IL-6,TNF-α,and BALP decreased time- and dose-dependently（P〈0.05）.The correlation analysis showed that PPARγ2 negatively correlated with IL-1β,IL-6 and TNF-α（-0.5 r 0,P〈0.05）.3） BMD decreased in ovariectomized group after the different doses of pioglitazone treatment（P〈0.05）.Conclusion 1） Rats in ovariectomized group show insulin resistance,and the levels of IL-1β,IL-6 and TNF-α increase.2）Pioglitazone activates transcriptional activity of PPARγ2 and raise its expression.Pioglitazone decreases high bone turnover rate due to PMOP by inhibiting the levels of osteoclasts-stimulating factors IL-1β,IL-6 and TNF-α,while increasing the insulin sensitivity and improving insulin resistance.Meanwhile,it suppresses and BALP level and inhibits bone formation.Overall

关 键 词：去卵巢大鼠 吡格列酮 骨密度 IL-1Β IL-6 TNF-Α 

分 类 号：R681[医药卫生—骨科学]