密骨胶囊调控ERK1和p38对骨质疏松大鼠骨形成的影响

Effect of Migu capsule regulating ERK1 and p38 on bone formation in ovariectomized rats

目的过观察密骨胶囊对骨质疏松大鼠骨形成标志物表达及细胞外调节蛋白激酶1(extracellular regulated protein kinase 1,ERK1)、p38丝裂原活化蛋白激酶(p38 mitogen-activated protein kinase,p38)表达,探讨密骨胶囊促骨形成的作用机制。方法选取3月龄清洁级健康雌性Wistar大鼠,采用切除卵巢手术建立骨质疏松模型。模型成功后,将卵巢切除大鼠随机分为模型组(OVX)和密骨胶囊组,同时将假切大鼠作为对照组。显微CT(micro-CT)扫描分析大鼠胫骨体积骨密度和骨微结构参数;荧光定量PCR(real-time quantitative PCR,qPCR)方法检测骨内骨碱性磷酸酶(bone alkaline phosphatase,BALP)、骨形态发生蛋白-2(bone morphogenetic protein-2,BMP2)、Ⅰ型胶原a1(collagen typeⅠalpha 1,COL1a1)、ERK1和p38 mRNA表达。结果micro-CT结果显示,大鼠卵巢切除后,模型组体积骨密度、骨体积分数、骨小梁厚度和骨小梁数量均明显低于对照组(P<0.05),骨小梁分离度明显大于对照组(P<0.05);密骨胶囊组体积骨密度、骨体积分数和骨小梁厚度均明显增加(P<0.05),骨小梁数量增加,但与模型组比较无统计学意义。密骨胶囊可上调骨质疏松大鼠骨内骨形成标志物mRNA表达,包括BALP、BMP2、COL1α1,亦可上调股骨内ERK1和p38 mRNA的表达。结论密骨胶囊可以升高骨质疏松大鼠骨密度,改善部分骨微结构,上调骨形成标志物的表达,其作用机制可能与调控ERK1、p38表达有关。

Objective To explore the mechanism of Migu capsule in promoting bone formation through the regulation of the expression of bone formation markers and the extracellular regulated protein kinase 1(ERK1)and p38 mitogen-activated protein kinase(p38)in ovariectomized rats.Methods The osteoporosis model was established by oophorectomy in healthy 3-month-old Wistar rats.After successful modeling,the rats were randomly divided into model group(OVX),Migu capsule group(MG),and sham group.Micro-CT scan was used to analyze the volume bone mineral density(BMD)and bone microstructure parameters of tibia.The mRNA expressions of bone alkaline phosphatase(BALP),bone morphogenetic protein-2(BMP2),collagen typeⅠalpha 1(COL1a1),ERK1 and p38 in bone were detected by qPCR.Results Micro-CT results showed that after ovariectomy,bone mineral density,bone volume fraction,trabecular thickness,and trabecular number in the model group were significantly lower than those in the sham group(P<0.05).Trabecular separation was significantly higher than that in the sham group(P<0.05).Bone mineral density,bone volume fraction,and trabecular thickness were significantly increased in Migu capsule group(P<0.05),and the trabecular number was increased,but there was no statistical significance compared with the model group.Migu capsule could up-regulate the mRNA expression of bone formation markers in ovariectomized rats,including BALP,BMP2,and COL1α1.Migu capsule could up-regulate the expression of ERK1 and p38 mRNA in bone.Conclusion Migu capsule can increase bone mineral density,improve bone microstructure and up-regulate the expression of bone formation markers in ovariectomized rats.The mechanism of action may be related to the regulation of ERK1 and p38 expression.