双醋瑞因对去卵巢大鼠骨量丢失的干预作用

Interventional effect of diacerein on bone mass loss in ovariectomized rats

背景:双醋瑞因是一种新型的白细胞介素1阻滞剂,对绝经后骨质疏松形成过程中的白细胞介素相关因子增强骨吸收的抑制作用目前的报道较少。目的:验证双醋瑞因对去卵巢大鼠骨量丢失的干预作用。设计、时间及地点:完全随机分组设计,随机对照实验,于2008-08/11在重庆医科大学实验动物中心实验室完成。材料:清洁级3月龄雌性SD大鼠40只,随机分为4组:假手术组、去卵巢组、双醋瑞因10,100mg/(kg·d)组,每组10只。双醋瑞因胶囊(每粒50mg含双醋瑞因48.1mg),为昆明积大制药有限公司生产,批号:20070532。方法:除假手术组外其他3组大鼠分离出双侧卵巢结扎输卵管血管后切除卵巢,假手术组只切除卵巢周围少量脂肪组织,逐层缝合皮肤。去卵巢术后第2天双醋瑞因10,100mg/(kg·d)组开始灌胃给药,假手术组和去卵巢组给予等量的生理盐水,持续给药10周后麻醉下处死所有大鼠采血,收集骨骼标本。主要观测指标:以骨密度双能X射线测量仪测量第3腰椎、股骨骨密度;放射免疫法测定骨组织中白细胞介素1β、白细胞介素6水平及血清骨钙素水平。结果:40只大鼠均进入结果分析。去卵巢组骨密度低于假手术组(P<0.05),双醋瑞因2个剂量组骨密度高于去卵巢组(P<0.05)。去卵巢组骨组织中白细胞介素1β、白细胞介素6水平高于假手术组(P<0.05);双醋瑞因2个剂量组骨组织中白细胞介素1β、白细胞介素6水平低于去卵巢组(P<0.05)。去卵巢组血清骨钙素水平高于假手术组(P<0.05);双醋瑞因2个剂量组血清骨钙素水平与去卵巢组相比,差异无显著性意义(P>0.05)。结论:雌性大鼠卵巢切除10周后骨量丢失明显,双醋瑞因对去卵巢后大鼠由于骨吸收增强所引起的骨量丢失有干预作用。对成骨细胞介导的骨形成无明显的影响。

BACKGROUND： Diacerein is a new kind of interleukin-1 block agent. Researches regarding intervention effect of interleukin correlation factor on increase of bone absorption in postmenopausal osteoporosis are few. OBJECTIVE： To investigate the intervention effect of diacerein on bone mass loss in ovariectomized （OVX） rats. DESIGN, TIME AND SETTING： The complete randomized controlled experiment was performed in the Laboratory of Experimental Animal Center of Chongqing Medical University from August to November 2008. MATERIALS： Forty female, 3-month-old, Sprague Dawley rats were randomly divided into sham operation, OVX, diacerein 10mg, 100 mg/（kg.d） groups, with 10 animals in each group. Anbiding capsule （contains 48.1 mg diacerein in each 50 mg capsule） was produced by Kunming Jida Pharmaceutical Co., Ltd, with batch number of 20070532. METHODS： All rats received ovariectomy exception the sham operation group. Rats of sham operation group were only received a little fatty tissue removal around the ovary, and sutured the skin. Diacerein was intragastric administrated at the second day after the ovariectomy in the diacerein 10mg, 100 mg/（kg·d） groups, equivalent volume of normal saline was administrated in the sham operation, OVX groups. Then all rats were killed under anesthesia to collect the blood and skeleton samples after 10 weeks continue medication. MAIN OUTCOME MEASURES： Bone mineral density of the right femur and the third lumbar vertebra were determined by Dual-Energy X-ray bone densitomatry. The levels of interleukin-1β, interleukin-6 in bone tissue and the level of serum osteoealcin were determined by radio-immunity assay. RESULTS： All rats were involved in the final analysis. The levels of bone mineral density in two diacerein groups were higher than that in the OVX group （P 〈 0.05）, which was lower in the OVX group than the sham operation group （P 〈 0.05）. The levels of intedeukin-1β, intedeukin-6 in bone tissue in the OVX group were higher than that of the sham operation group （P 〈 0.05）, which was lower in two diacerein groups than that in the OVX group （P 〈 0.05）. Compared with the sham operation group, the level of serum esteocalcin in the OVX group was higher （P 〈 0.05）. The differences of serum osteocalcin levels between OVX group and two diacerein groups had not statistically difference （P 〉 0.05）. CONCLUSION： The bone loss is obviously 10 weeks later after ovariectomy. Diacerein has intervention effect on bone loss induced by increase of bone absorption in OVX rats, which have no significant effects on bone formation mediated by osteoblast.