雌激素受体和过氧化物酶增殖子激活受体γ交叉对话对大豆苷原骨的保护作用

Role of the cross-talk between estrogen receptors and peroxisome proliferator-activated receptor gamma in daidzein＇s prevention and treatment of osteoporosis in ovariectomized rats

目的探讨雌激素受体（ERs）和过氧化物酶增殖子激活受体γ（PPARγ）交叉对话对大豆苷原防治去势大鼠骨质疏松的作用。方法将4个月龄大鼠随机分为6组：假手术组、去势组、去势＋戊酸雌二醇组（E：）、去势＋高剂量大豆苷原组（H—Dai，200mg·kg^-1·d^-1）、去势＋中剂量大豆苷原组（M—Dai，50mg·kg^-1·d^-1）和去势＋低剂量大豆苷原组（L-Dai，10mg·kg^-1·d^-1），造模成功后，灌胃3个月后处死大鼠。以腰椎k和右股骨提取总RNA，RT—PCR方法检测ERa、ER13和PPA脚mRNA表达；免疫组化检测腰椎L4与左股骨3种蛋白表达。结果不同剂量大鼠ERocmRNA和蛋白表达水平均显著低于ER13。除H—Dai组大鼠股骨之外，ER13mRNA在M—Dai组大鼠腰椎和股骨（0．0177±0．0010，0．0245±0．0013）和L—Dai组大鼠的腰椎及股骨（0．0276±0．0027，0．0278±0．0044）以及H—Dai组大鼠腰椎（0．0163±0．0037）的表达水平均显著高于去势组（0．0016±0．0005，0．0041±0．0014），且与E：组差异无统计学意义，ER13蛋白的表达情况与之类似。组间比较显示随着大豆苷原剂量降低，ER13mRNA及蛋白表达水平有增高的趋势，而PPARγmRNA及蛋白表达水平则降低。结论ER13和PPARγ之间存在此消彼涨的交叉对话关系，可能参予介导大豆苷原防治去势大鼠骨质疏松症的量效作用。

Objective To investigate the role of the cross-talk between estrogen receptors and peroxisome proliferator-activated receptor gamma in daidzein＇s prevention and treatment of osteoporosis in the ovariectomized rats. Methods Sixty four-month-old Sprague-Dawley （SD） female rats were divided into six groups. Four weeks after the establishment of osteoporosis model, the ovariectomized rats were administered different drugs by gavage respectively for three months. After sacrificeing, the expressions of mRNA of ERα, ERβ and PPART in L6 and right femur were measured by reahime-RT-PCR, while proteins were detected by immunohistochemistry. Results The expressions of ERa mRNA and protein were significantly lower than that of ERβ in three dosing groups. Excepting that of rat femur of rats in H-Dai group, the expressions of ERβ mRNA of lumbar spine and femur in M-Dai group （0. 0177 ± 0. 0010, 0. 0245 ± 0. 0013 ） and L-Dai groups （0. 0276 ±0. 0027, 0. 0278 ±0. 0044） and lumbar spine in H-Dai group （0. 0163 ±0. 0037） were significantly higher than that in OVX group （0. 0016 ±0. 0005, 0. 0041 ±0. 0014）. There was no significant difference with E2 group. At the same time, the expression of ERβ protein showed into the similar trend as that of mRNA. And there was an rising expressions of ERβ while daidzein dose decreased. On the contrary, the expressions of PPARγ mRNA and protein decreased. Conclusions There is an inverse cross-talk relationship between ERβ and PPARγ, it may play a role in daidzein＇ s prevention and treatment of osteoporosis in ovariectomized rats.