中药骨康灵联合同位素药物锝-99-亚甲基二膦酸钠治疗兔骨质疏松的实验研究

目的：探讨自制煎方骨康灵联合非放射性同位素药物锝-99-亚甲基二膦酸钠 （ technetium [^99Tc] methylene diphosphonate injection, ^99Tc-MDP） 治疗骨质疏松症的优越性。方法：肌肉注射盐酸地塞米松针剂（dexamethasone．DX）制作龟骨质疏松模型，将实验免分为8组：A,B组为正常对照组；C、D组为骨质疏松对照组；E组为”Tc-MDP治疗组；F组为氯基二膦酸盐治疗组；G组为单用骨康灵治疗组；H组为m，Tc-MDP联合骨康灵治疗组。A、C组实验兔于实验第8周处死,以证实骨质疏松模型成立。E、F、G、H组实验兔于治疗16周后与B、D组一起处死，行病理细胞学分析、骨形态计量分析、骨密度检测、生物力学试验、X线摄片、CT摄片、核素骨骼扫描以及血清骨碱性磷酸酶 （bone alkaline phosphatase. BALP）和骨钙素（骨谷氧酸蛋白）（bone gla protein．BGP）的测定。结果：实验兔连续肌肉注射DX8周后,A组实验兔骨小梁排列规则。呈正常骨组织形态。C组实验兔骨小梁排列稀疏。存在较明显的骨小梁断裂现象，呈骨组织破坏形态，同时A、C两组在骨密度、骨生物力学、骨形态计量等方面的差异．均有统计学意义。实验室检查结果显示．兔骨质疏松动物模型成立。实验第9周对E组、F组、G组、H组实验兔进行治疗。细胞病理切片显示，D组实验兔骨小梁明显稀疏，有断裂和缺损区或凹陷。B组骨小梁排列均匀、规则，H、E组的细胞学表现为在骨质疏松的基础上骨质和骨小梁明显得到了修复，骨小梁增粗，F组实验兔的细胞学表现则优于G组，G组又略优于D组，H、E组更明显优于D组。结论：骨康灵与具有高亲骨特异性调节骨代谢作用的同位素药物^99Tc-MDP联合治疗龟实验性骨质疏松的教果明显优于单独治疗。

Experimental study of Gukangling Decoction combined with technetium [99Tc] methylene diphosphonate injection in treating osteoporotic rabbits

OBJECTIVE: To evaluate the advantage of Gukangling Decoction (GKLD), a compound traditional Chinese herbal medicine, combined with technetium [(99)Tc] methylene diphosphonate injection ((99)Tc-MDP) in treating osteoporosis in rabbits. METHODS: A rabbit model of osteoporosis was established by intramuscular injection of dexamethasone (DX). Fifty-six rabbits were divided into 8 groups: Group A, B, C, D, E, F, G and H. Rabbits in groups A and B were intramuscularly injected normal saline as normal control, groups C and D were untreated groups, rabbits in group E were treated by (99)-MDP, rabbits in group F were treated by aminodiphosphate, rabbits in group G were treated by GKLD, and rabbits in group H were treated by (99)-MDP and GKLD. Rabbits in groups A and C were executed to demonstrate the establishment of the rabbit model of osteoporosis at the 8th week of experiment. Rabbits in the other six groups were executed after 16-week experiment (8-week treatment), and then bone structure and cell shape were observed by electron microscope, X-ray, CT and emission computed tomography (ECT). Bone density, biomechanical parameters, the levels of bone specific alkaline phosphatase (BALP) and bone Gla protein (BGP) were measured too. RESULTS: After 8-week of intramuscular injection of DX, the bone trabecula in group A were regular and showed normal configuration, while the bone trabecula in group C were sparse, ruptured and showed damaged form. The bone density and biomechanical parameters in group A were higher than those in group C, indicating that the rabbit model of osteoporosis was established successfully. At the 9th week of experiment, the results of cell pathology in group D showed that the bone trabeculas were sparse, ruptured, defected or had hollow section, but the bone trabeculas in group B were regular and dense. The bone trabeculas in groups H and E were restored, and were thicker than those in group D. The bone quality in groups H and E was better than group D significantly, the bone quality in group F was better than group G, and the bone quality in group G was better than group D slightly. CONCLUSION: GKLD combined with (99)-MDP had superiority in treating osteoporosis of rabbits as compared with the respective single therapy.