应用双氯芬酸钠后骨质疏松性骨折大鼠的肝肾变化:组织学验证

背景:临床上常用非类固醇类抗炎药治疗骨质疏松症和骨质疏松性骨折引起的疼痛,文献报道非类固醇类抗炎药会引起肝肾功能的损害,但其究竟如何影响肝肾组织尚不清楚.目的:观察双氯芬酸钠对骨质疏松性骨折大鼠肝肾组织的影响.设计、时间及地点:随机对照动物实验,于2007-08/2008-02在上海中医药大学动物实验中心完成.材料:8月龄雌性SD大鼠24只,体质量300-320 g,随机分为生理盐水组、双氯芬酸钠先骨折后药物组和双氯芬酸钠先药物后骨折组,每组8只.方法:大鼠卵巢去势后饲养3个月,建立骨质疏松模型,随机分组.生理盐水组和先骨折后药物组先进行双侧股骨中段骨折造模,再分别灌注生理盐水10 mL/(kg·d)和双氯芬酸钠5 mg/(kg·d).1次/d,共3周;先药物后骨折组先灌注双氯芬酸钠5 mg/(kg·d)3周,再进行骨折造模.主要观察指标:分别于骨折后2,3,4,6周摘取肝脏和双侧肾脏,行苏木精-伊红染色观察.各组大鼠肝脏和肾脏组织学观察.结果:双氯芬酸钠先骨折后药物组肾小球炎症反应;肾小管管腔扩张,上皮细胞水肿,细胞核消失,小管变性坏死,管腔内出现白细胞及细胞碎片和药物结晶;肾间质充血,炎症细胞浸润.双氯芬酸钠组肝小叶结构模糊,肝细胞肿胀,脂肪变性,部分肝细胞坏死:汇管区炎症反应;中央静脉和肝窦隙淤血.双氯芬酸钠先药物后骨折组同样造成肝肾组织损害,持续3周左右.结论:双氯芬酸钠对骨质疏松性大鼠的肝肾组织有一定损害,尤其是肾脏组织.长时间应用双氯芬酸钠造成的肝肾组织损害是不可逆的.

Changes in liver and kidney following treatment with diclofenac sodium in osteoporotic fracture rats: A histological verification

BACKGROUND: The pain caused by osteoporosis and osteoporotic fracture is usually treated with non-steroidal anti-inflammatory drugs (NSAIDs) in clinic, which has been reported that dysfunction of liver and kidney will follow the use, but what has happened in the tissue of liver and kidney is not reported. OBJECTIVE: To study the effect of NSAIDs on the tissue of liver and kidney in osteoporotic fracture rats. DESIGN, TIME AND SETTING: Randomized controlled animal experiment. The experiment was completed in the Animal Experiment Center in Shanghai University of Traditional Chinese Medicine from August 2007 to February 2008.MATERIALS: A total of 24 female SD rats, 8-month-old, weighing 300-320 g, were randomly divided into 3 groups, saline group,diclofenac sodium (fracture before medicine) group and diclofenac sodium (fracture after medicine) group, with 8 rats in each group.METHODS: The rats were housed for 3 months after ovariectomized to establish osteoporosis models. Rats in the saline group and diclofenac sodium (fracture before medicine) group were administrated saline and diclofenac sodium after transverse osteotomy at the middle shaft of bilateral femur respectively; in the diclofenac sodium (fracture after medicine) group were femur.MAIN OUTCOME MEASURES: The histological observation of liver and kidney was performed at weeks 2, 3, 4 and 6 after fracture.RESULTS: In the diclofenac sodium (fracture before medicine) group, diclofenec sodium caused the inflammatory response at glomeruli, which exhibited expansion of tubular lumen, edema of epithelial cells, disappeared cell nuclei, degeneration and necrosis of renal tubule, cell debris and drugs crystals accumulated in the tubular lumen, congestion and inflammatory cell infiltration of renal interstitium. Administrating diclofenac sodium may cause the inflammatory response at portal area, indistinct structure of hepatic Iobule, hepatic cells edema, steatosis and necrosis. Administrating diclofenac sodium before osteoporotic fracture also resulted in tissue lesions in kidney and liver, the damage would continue about 3 weeks.CONCLUSION: The diclofenac sodium cause histological lesions of kidney and liver in osteoporotic rats, especially in kidney. The histological lesions of kidney and liver are inreversible after administrating diclofenac sodium for a long time.