甘草酸对小鼠肝纤维化性骨丢失的防治作用及机制探讨

甘草酸对小鼠肝纤维化性骨丢失的防治作用及机制探讨
邹丽宜;吴铁;崔燎
【期刊名称】《中国组织工程研究》
【年(卷),期】2005(009)007
【摘要】BACKGROUND: Since chronic liver disorders are associated with bone loss commonly, it is very significant to probe into the prevention of such bone loss for the treatment of osteoporosis.OBJECTIVE: To study the mechanism of glycyrrhizic acid on prevention and treatment of bone loss induced by liver fibrosis in mice.DESIGN: Randomized and controlled study in which the experimental animals were taken as the objects.SETTING: Experimental animal center, central experimental room and pharmacological research room of a universityMATERIALS: The experiment was performed from January to September 2001. Forty common-grade PCR mice of either sex were employed, weighted varied from 20 to 22 g, provided by Experimental Animal Center of the Institution. According to mass-equivalence principle, 4 groups were randomized, named as control, model group, the treatment with colchicine group(CL group) and the treatment of glycyrrhizic acid group(GA group-) with 10 mice in each group.METHODS: Except the control group, in the model group, CL group and GA group, the subcutaneous injection with 400 g/L carbon tetrachloride prepared with peanut oil was given for 5 weeks to induce liver fibrosis in mice. Afterward, the treatment was applied with carbon-
tetrachloride peanut-oil solution 10 mL/kg, colchicum autumnale solution 0. 1 g/kg and glycyrrhizic acid solution 0. 1 mg/kg successively. At the end of the experiment, the eyeball was extirpated for blood collection. The serum was separated to assay the various relevant biochemical indexes of liver injury, observe the changes in liver pathological tissues and measure bone calcium(Ca2+) content of femur and the contents of other bone trace elements as well as bone oxyproline hydroxyproline (Hyp).Effects of glycyrrhizic acid on the contents of bone trace elements in mice of every group.RESULTS: The levels of serum aspartate aminotransferase(AST) and alanine aminotransferase(ALT) in CL group and GA group were lower than those in the model group( P < 0. 01 ). The level of albumin and ratio between albumin and globulin in the model group were lower than those in CL group and GA group( P < 0.01, P < 0.05) . The content of bone calcium in CL group and GA group were lower than that in the control group ( P < 0. 05),but that was higher than the model group( P < 0.05) . The unit contents of copper(Cu2+ ), magnesium(Mg2+) and zinc(Zn2+) in the right femur of the model group were all higher than the control group ( P < 0.01 ), but the contents of those in GA group were not indicated significant differences compared with the control group ( P > 0.05 ). The liver pathological changes of mice in GA group were obviously milder compared with the model group ( P < 0.01 ) and it was shown with VG staining the severity of hyperplasia of liver collagenous fibers was remarkably milder compared with the model group( P <
0.01).CONCLUSION: The extractive solution of glycyrrhizic acid induces
medical metabolic enzyme in the liver, enhances detoxification of liver, protects liver to maintain protein metabolic level and maintains the normal metabolism of bone to promote bone Ca2+ and balance between oxyproline hydroxyproline (Hyp) and trace elements of bone so as to prevent and treat bone loss.%背景:慢性肝病患者常常伴有骨质的丢失,因此探讨预防此种骨丢失对防治此类患者的骨质疏松极有意义.目的:研究甘草酸对肝纤维化小鼠骨丢失的防治作用及机制.设计:以实验动物为研究对象的随机对照研究单位:一所大学的实验动物中心、中心实验室和药理研究室材料:本实验于2001-01/2001-09进行,选择普通级PCR小鼠40只,由本院实验动物中心提供,体质量20～22 g,雌雄各半,按质量对等原则随机分为4组,即对照组、模型组、秋水仙组和甘草酸组,每组10只.方法:除对照组外,模型组、秋水仙组和甘草酸组均予400 g/L四氯化碳花生油皮下注射5周致小鼠肝纤维化,然后分别应用四氯化碳花生油溶液10
mL/kg、秋水仙溶液0.1 g/kg和甘草酸溶液0.1 mg/kg进行防治,实验结束时摘眼球取血,分离血清检测与肝损伤相关的各种生化指标,观察肝脏病理组织变化以及测定股骨的骨钙(Ca2+)量和其他骨微量元素以及骨羟脯胺酸的含量.主要观察指标:①甘草酸对各组小鼠肝损伤后血清生化指标的影响;②甘草酸对各组小鼠肝脏病理改变的的影响;③甘草酸对各组小鼠骨质的影响;④甘草酸对各组小鼠骨微量元素含量的影响.结果:秋水仙组和甘草酸组小鼠的血清谷草转氨酶(AST)、谷丙转氨酶(ALT)比模型组低(P<0 01);模型组的白蛋白、白蛋白/球蛋白值比秋水仙组和甘草酸组低(P<0.01,P<0.05);秋水仙组和甘草酸组的骨钙含量低于对照组(P<0.05),但比模型组高(P<0.05);模型组右股骨单位骨重铜、镁和锌的含量均比对照组高
(P<0.01),而甘草酸组的含量与对照组的差异无显著性意义(P>0.05);甘草酸组小鼠肝脏病理改变明显比模型组轻(P<0.01),VG染色可见胶原纤维增生程度明显比模型组轻(P<0.01).结论:甘草酸提取液能诱导肝药酶,增强肝脏解毒作用;保护肝脏,维持
蛋白代谢水平;维持骨的正常的代谢,促进骨Ca2+和骨羟脯氨酸以及骨微量元素的平衡,防治骨丢失.
【总页数】3页(P217-219)
【作者】邹丽宜;吴铁;崔燎
【作者单位】广东医学院药理教研室,广东省,湛江市,524023;广东医学院药理教研室,广东省,湛江市,524023;广东医学院药理教研室,广东省,湛江市,524023
【正文语种】中文
【中图分类】R681
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