补肾壮骨颗粒对去卵巢大鼠血清GH和IGF-1及其骨组织中受体表达的影响*

目的:探讨补肾壮骨颗粒对去卵巢大鼠血清生长激素(GH)和胰岛素样生长因子-1(IGF-1)及其骨组织中相关受体表达的影响。方法:SD未育雌性大鼠48只(体重273.0±21.3g),分为4组,补肾壮骨颗粒组(BSZG组)给药量为2.5 g/(kg·d),戊酸雌二醇组(E2组)给药量为0.071 mg/(kg·d),假手术组(SHAM组)及去卵巢模型组(OVX组)灌服等量生理盐水。每组各12只,每日干预1次。分别干预3个月、6个月后各取半数,活体采用骨密度仪检测骨密度(BMD)后进行取材,ELISA法检测血清GH和IGF-1,qPCR法检测骨组织GHR及IGF-1R,Image J软件分析垂体GH免疫组化片OD值和阳性细胞计数。结果:①干预3个月后,与SHAM组相比,OVX组腰椎及脊柱BMD均下降(P＜0.05),两药物干预组未见明显差异(P＞0.05);与OVX组相比,BSZG组两部位BMD及E2组脊柱BMD均有所上升(P＜0.05),但两药物干预组比较差异无统计学意义(P＞0.05)。干预6个月后,与SHAM组相比,OVX组腰椎及脊柱BMD均有下降(P＜0.05),两组药物干预组BMD无明显下降(P＞0.05);与OVX组相比,两药物干预组脊柱及股骨BMD均上升(P＜0.05),但两药物干预组组间比较差异无统计学意义(P＞0.05)。②两阶段干预后,与OVX组相比,BSZG组血清GH及IGF-1、骨组织GHR及IGF-1R的表达水平均上升(均P＜0.05);E2组血清GH和左侧胫骨两受体表达水均上升(P＜0.05),但血清IGF-1水平不变(P＞0.05)甚至下降(P＜0.05)。③两阶段干预后,与SHAM组相比,OVX组光密度值及阳性细胞计数均有下降(P＜0.05);与OVX组相比,两药物干预组光密度值和阳性细胞数均有上升(P＞0.05)。④Pearson相关分析显示:血清GH、IGF-1浓度及其骨组织受体与BMD呈正相关。血清GH浓度与光密度值及阳性细胞数呈正相关。结论:补肾壮骨颗粒可提高去卵巢骨质疏松大鼠血清GH、IGF-1及其骨组织中受体的表达水平,防止骨量的进一步丢失和增加骨密度。

Effects of Bushen Zhuanggu Granules on expressions of serum GH with IGF-1 and its receptors in bone tissue of ovariectomized rats

Objective: To investigate the effects of Bushen Zhuanggu granule on the expressions of serum growth hormone (GH) and insulin-like growth factor-1(IGF-1) and their receptors in bone tissues of ovariectomized rats. Methods: Forty-eight SD female rats (weight 273±21.3 g) were divided into 4 four groups: the dosage of Bushen Zhuanggu granule group (BSZG) was 2.5 g/(kg·d),the do -sage of estradiol group(E₂) was 0.071mg/(kg·d),sham group (SHAM) and ovariectomized model group (OVX group) were given the same amount of saline by oral administration.Each group included 12 rats,the treatments were conducted once a day. After 3 and 6 months of treatment,bone mineral density (B -MD) was measured by bone density instrument;the serum levels of GH and IGF-1 were detected by EL-ISA;the expressions of GHR and IGF-1R of bone tissue were detected by qPCR;the optical density(OD)value and positive cell count of pituitary GH immunohistochemical tablets were analyzed by Image J software,respectively. Results: ①After 3 months intervention,compared with the SHAM, the BMD of the spine in E₂ group was increased(P＜0.05),and the BMD of both parts in BSZG group were increased(P＜0.05).After two stage intervention,BMD of both part in the two drug groups was higher than that in the OVX group(P＜0.05).②After two-stage intervention,the expression levels of serum GH and IGF-1,GHR and IGF-1R in BSZG group were higher than those in OVX group (P＜0.05).The levels of serum GH and it's receptors in the E₂ group were increased (P＜0.05), but the serum IGF-1 level remained unchanged (P＞0.05) or even was decreased (P＜0.05).③After two stage in -tervention,the OD values and the positive cells count in the two drug intervention groups were increased (P＞0.05).④Pearson correlation analysis showed that serum GH,IGF-1 concentration and it's receptors in bone tissue were positively related with BMD. Serum GH concentration was positively correlated with OD values and number of positive cells. Conclusion: Bushen Zhuanggu granule can be used to improve the expressions of GH,IGF-1 in serum and its receptors in bone tissues of ovariectomized osteoporosis rats to prevent further loss of bone mass and increase bone mineral density.