甲状旁腺素(1-34)对卵巢切除大鼠腰椎间盘退变MMP-1及MMP-13表达的影响

The effect of parathyroid hormone(1-34) on the expressions of MMP-1 and MMP-13 in the intervertebral disc on an ovariectomized rat model

目的探讨甲状旁腺素(parathyroid hormone,PTH)(1-34)对卵巢切除(ovariectomy,OVX)大鼠腰椎间盘退变中基质金属蛋白酶1(matrix metalloproteinase-1,MMP-1)及MMP-13表达的影响。方法 3月龄雌性SD大鼠30只随机分为3组:假手术(Sham)组、卵巢切除(OVX)组及卵巢切除+PTH(1-34)(OVX+PTH)组各10只。OVX组及OVX+PTH组行双侧卵巢切除术后12周,OVX+PTH组大鼠给予皮下注射PTH(1-34)30μg·kg-1·d-1。连续用药12周后,处死大鼠并收集标本。对L3椎体进行骨密度(bone mineral density,BMD)检测,对L4~5椎间盘行组织学观察及免疫组织化学染色分析。结果卵巢切除术后24周,OVX组椎体BMD显著低于Sham组,OVX+PTH组椎体BMD显著高于Sham组和OVX组。OVX组MMP-1及MMP-13显著高于Sham组(P<0.05),OVX+PTH组MMP-1显著低于OVX组(P<0.05),而MMP-13与OVX组比较差异无统计学意义(P>0.05)。结论皮下注射PTH(1-34)可有效抑制卵巢切除大鼠退变椎间盘中MMP-1及MMP-13的表达。

Objective To investigate the effects of parathyroid hormone(PTH)(1-34)on the expressions of matrix metalloproteinase-1(MMP-1)and MMP-13 in the intervertebral disc on an ovariectomized(OVX)rat model.Methods Thirty female Sprague-Dawley rats,3 month of age,were randomly divided into three groups:the sham-operated(Sham)group and two ovariectomized groups treated with vehicle or PTH(1-34)(30μg·kg-1·d-1)for twelve weeks.Treatment was started after twelve weeks post-OVX and continued for twelve weeks.At the end of experiment,bone mineral density(BMD),histology and immunohistochemistry analysis were performed to all groups.Results Twenty four weeks after OVX,the BMD values of L3 vertebral bodies in the OVX group were significantly decreased,compared with the Sham group(P<0.05).The BMD values in the OVX+PTH group were significantly increased,compared with the Sham group and OVX group(P<0.05).Immunohistochemistry analysis revealed a significant increase in matrix metalloproteinase(MMP)-1 and MMP-13 expression,compared with the Sham group(P<0.05),the expression of MMP-1 was significantly decreased(P<0.05),and no significant difference in MMP-13 expression in the OVX+PTH group(P>0.05),compared with the OVX group.Conclusion PTH(1-34)treatment was effective in reducing the expression of MMP-1 and MMP-13 in the degenerated disc in OVX rats.