补肾方对骨质疏松模型大鼠骨密度及胰岛素样生长因子Ⅰ和肿瘤坏死因子α的影响

Effects of Chinese herbs of tonifying kidney on bone mineral density and contents of insulin-like growth factor-1 and tumor necrosis factor-alpha in osteoporotic rats

背景:研究证实,胰岛素生长因子和肿瘤坏死因子α分别具有调节成骨细胞和破骨细胞功能。目的:实验拟验证补肾复方中药对骨质疏松模型大鼠骨密度及胰岛素样生长因子Ⅰ、肿瘤坏死因子α的影响。设计、时间及地点:随机对照动物实验,于2006-09/2007-03在广州中医药大学动物中心和广州中医药大学附属骨伤科共同完成。材料:选择SPF级6月龄健康雌性SD大鼠68只,体质量约260～280g。随机分为空白组和手术组,分别为22只和46只。术后3个月后从两组随机各选出10只以确定造模成功。造模后大鼠随机分为3组,模型组、雌激素组、中药组各12只。剩余12只为空白对照组。补肾中药主要由淫羊藿、补骨脂、丹参、黄芪等10味中药组成,含生药量为1430g/L,由广州中医药大学附属骨伤科医院制剂室提供。方法:中药组给予补肾中药按4.8g/kg灌胃,1次/d;雌激素组给予尼尔雌醇按1mg/kg灌胃,1次/周;模型组和空白组给予蒸馏水按10mL/kg灌胃,1次/d,连续治疗3个月。主要观察指标:分别测量各组大鼠全身骨密度、腰椎骨密度、双髋部骨密度,以及外周血清中的胰岛素样生长因子Ⅰ、肿瘤坏死因子α及雌激素含量。结果:最后进入结果分析64只。①造模组全身骨密度低于空白组(P<0.05)。②治疗后,中药组和雌激素组的全身骨密度、腰椎骨密度高于模型组(P<0.05),中药组和雌激素组比较,差异无显著性意义(P>0.05)。③与模型组比较,中药组能显著降低肿瘤坏死因子α水平和提高雌激素水平(P均<0.05),与雌激素组比较差异无显著性意义;中药组还能提高胰岛素样生长因子Ⅰ的含量(P<0.05),雌激素组胰岛素样生长因子Ⅰ水平明显均低于其余3组。结论:中药补肾复方在治疗骨质疏松的过程中类雌激素样作用可能是其主要作用机制,但其对胰岛素样生长因子Ⅰ的影响不同于雌激素。

BACKGROUND： Studies have shown that insulin growth factor and tumor necrosis factor a （TNF- a ） can regulate osteoblast and osteoclast. OBJECTIVE： To explore the effect of Chinese medicine prescription of tonifying kidney on bone mineral density, insulin-like growth factor-I （IGF-I） and TNF- a in osteoporotic rats. DESIGN, TIME AND SETTING： Randomized controlled animal trial was performed at Animal Center and Orthopedic Hospital of Guangzhou University of Chinese Medicine from September 2006 to March 2007. MATERIALS： Sixty-eight SPF 6-month-old healthy female SD rats weighing 260 -280 g were randomly divided into normal group （n=22） and model group （n=46）. Three months after surgery, 10 rats from each group were selected to confirm modeling. The other rats in ovariectomized group were randomly divided into 3 groups （n=12）： ovariectomized group （OVX）, estrogen group, and traditional Chinese herb group. The other 12 rats in the normal group served as control group. The traditional Chinese herb consisted of Yinyanghuo, Buguzhi, Danshen, Huangqi and other six kinds of herbs containing crude drug of 1 430 g/L, prepared by Manufacturing Laboratory of Orthopaedic Hospital of Guangzhou University of Chinese Medicine. METHODS： The rats of traditional Chinese herb group were intragastrically administrated with herbs （4.8 g/kg）, once a day. The rats of estrogen group were intragastrically infused nilestriol （1 mg/kg）, once a week. The others were given distilled water （10 mL/kg）, once a day. The administration lasted for 3 months. MAIN OUTCOME MEASURES： Total body, lumbar vertebral and hip bone mineral density （BMD） was measured by dual energy X-ray absorptiometry, and the content of IGF- 1, estrogen and TNF： a in blood serum were detected with radioimmunoassay. RESULTS： Sixty-four rats were included in the final analysis. The BMD of OVX group was significantly decreased compared with the control group （P 〈 0.05）. After treatment, the BMD of the total body and lumbar vertebrae in the rats of Chinese herb and estrogen groups were significant higher than OVX group （P 〈 0.05）, but there were no significant differences between Chinese herb and estrogen groups （P 〉 0.05）. Compared with OVX group, Chinese herbs markedly reduced TNF- a levels, and increased IGF-1 and estrogen content （P 〈 0.05）, but there were no significant differences compared with estrogen group. Estrogen content in estrogen group was significantly lower than the other groups. CONCLUSION： Chinese medicine prescription of tonifying kidney plays estrogen-like role in treating osteoporosis, but has different influence on IGF-1 from estrogen.