摘要
目的 探讨二膦酸盐对糖皮质激素诱导的骨质疏松过氧化物酶体增殖物激活受体γ（PPARγ）表达的影响.方法 ①22例系统性红斑狼疮（SLE）患者,治疗组9例（标准剂量激素＋阿仑膦酸钠）,对照组13例（标准剂量激素）,24周后行骨髓穿刺术,检测免疫组织化学PPARγ平均积分吸光度.②采用原代人骨髓基质干细胞（hMSCs）培养,模拟髓内骨髓基质干细胞分化为脂肪细胞的过程,在相同条件下,分为成脂诱导组、成脂诱导＋10-5mol/L二膦酸盐组（高剂量组）、成脂诱导＋10-7mol/L二膦酸盐组（中剂量组）、成脂诱导＋10-9mol/L二膦酸盐组（低剂量组）干预诱导成脂过程,6～9 d后进行油红0染色、异丙醇萃取油红染料,515 nm测定各组吸光度（A）来反映成脂程度,定量聚合酶链反应（PCR）测定各组PPARγmRNA的表达水平.采用t检验和单因素方差分析法进行数据分析.结果 二膦酸盐治疗组免疫组织化学PPARγ平均积分吸光度较对照组减少（P＜0.05）;在诱导培养7 d后,成脂诱导组的A与低剂量组差异无统计学意义（P值0.167）,高剂量组、中剂量组A与成脂诱导组之间差异有统计学意义（P值分别为0、0.041）.定量PCR结果显示：高剂量组、中剂量组PPARγ mRNA的表达低于成脂诱导组（P值分别为0、0.01）,低剂量组与成脂诱导组之间差异无统计学意义（P＞0.05）.结论 有效浓度的二膦酸盐可以抑制PPARγ的表达,从而抑制hMSCs向脂肪细胞分化,抑制糖皮质激素诱导的骨质疏松症.
Objective To investigate the effects of bisphosphonate on the proliferator-activated receptor γ（PRARγ）expression of glucocorticoid-induced osteoporosis. Methods ① Twenty-two cases of systemic lupus erythematosus（SLE）patients with glucocorticoids（〉0.5 mg·kg-1 ·d-1）were divided into 2 groups： 9 cases in the treatment group in which patients received alendronate 70 mg qw., 13 cases in the control group without anti-osteoporosis treatment. All of the patients had bone marrow puncture after 24 weeks, bone tissues were embedded, sliced, and the value of average optical density of PPARγwas tested with immunohistochemistry. ② Human bone mesenchymal stem cells were cultured in the same conditions and stimulated to adipocytes. During the adipogenic process, the cells were divided into four groups, three of which were experimental groups treated with 10-5 mol/L（high-dose group）, 10-7 mol/L（medium-dose group）and 10-9 mol/L（low-dose group）bisphosphonate respectively, while the other was the control group without bisphosphonate in the medium. The adipocytes were identified by oil Red O stain seven days later. The adipocyte rate was measured by light absorption at 515 nm. The expression of PPARγ was measured by quantitative PCR. Comparisons between groups were tested by One-Way ANOVA analysis and t test. Results The average optical density of PPAR-gamma immunohistochemistry in the treatment group was less than the control group（P〈0.05）. Seven days later, the absorbance between adipogenic induction group and low-dose group was not significant（P=0.167）. but the adipogenic absorbance between the high-dose group, middle dose group and the control groups（P values were 0, 0.041）. There was significant difference in the quantitative PCR results between the high-dose group, middle dose group and the expression of PPARγ adipogenic induction group（P value was 0, 0.01）, but there was no significant differences between the low-dose group and adipogenic induction group（P〉0.05）.
出处
《中华风湿病学杂志》
CAS
CSCD
北大核心
2010年第11期743-745,共3页
Chinese Journal of Rheumatology
