芹菜素治疗去卵巢骨质疏松模型大鼠的作用与剂量

文题释义： 芹菜素：主要存在于瑞香科、马鞭草科、卷柏科植物中，如芫花，卷柏中含量较大。芹菜素属于黄酮类，具有抑制致癌物质的致癌活性；作为治疗HIV和其他病毒感染的抗病毒药物；MAP激酶的抑制剂；治疗各种炎症；抗氧化剂；镇静、安神；降压。与其他黄酮类物质(槲皮素、山奈黄酮)相比具有低毒、无诱变性等特点。 骨密度：全称是骨骼矿物质密度，是骨骼强度的一个重要指标，以g/cm³表示，是一个绝对值。在临床使用骨密度值时由于不同的骨密度检测仪的绝对值不同，通常使用T值判断骨密度是否正常。T值是一个相对值，正常参考值在-1和+1之间。当T值低于-2.5时为不正常。骨密度，是骨质量的一个重要标志，反映骨质疏松程度，预测骨折危险性的重要依据。 背景：研究证实芹菜素具有抗病毒、抗炎、抗氧化、镇静安神等功效。 目的：研究不同剂量芹菜素对大鼠骨质疏松的疗效并探讨其机制。 方法：实验方案经南方医科大学动物实验伦理委员会批准。成年雌性SD大鼠42只，通过卵巢切除法建立大鼠骨质疏松模型，实验分为7组，每组6只大鼠，分别为假手术组、芹菜素20，40，60和80 mg/kg组、对照组、阳性对照组。假手术组未摘除卵巢，阳性对照组每天灌胃烯雌酚(0.02 mg/kg)、维生素D和钙；对照组给予同等量纯净水皮下注射；芹菜素各组分别给予相应剂量的芹菜素皮下注射；1次/d，用药8周。分别检测干预后第4周和第8周大鼠股骨密度和血清中钙、磷、骨碱性磷酸酶、Ⅰ型前胶原氨基末端前肽、β-Ⅰ型胶原C-末端肽的水平。 结果与结论：①与对照组比较，芹菜素剂量为40，60和80 mg/kg时，大鼠的骨密度、血清中钙、磷在第4周和第8周时均较高(P < 0.05)，Ⅰ型前胶原氨基末端前肽、β-Ⅰ型胶原C-末端肽、骨碱性磷酸酶较低(P < 0.05)；②与阳性对照组比，芹菜素剂量为60 mg/kg和80 mg/kg时，大鼠的骨密度、血清中钙、磷和骨碱性磷酸酶、Ⅰ型前胶原氨基末端前肽、β-Ⅰ型胶原C-末端肽在第4周和第8周时均无明显差别(P > 0.05)，剂量为 20 mg/kg和 40 mg/kg时，骨密度、血清中钙、磷、均比阳性对照组低(P < 0.05)，Ⅰ型前胶原氨基末端前肽、β-Ⅰ型胶原C-末端肽比阳性对照组高(P < 0.05)；③对照组和假手术组比较，在第4周和第8周时大鼠骨密度、 血清中钙、磷均比较低(P < 0.05)，Ⅰ型前胶原氨基末端前肽、β-Ⅰ型胶原C-末端肽均比较高(P < 0.05)；④结果说明，去卵巢法建立大鼠骨质疏松模型确实有效；芹菜素对骨质疏松的治疗作用和剂量相关，一定剂量的芹菜素具有类似烯雌酚样的抗骨质疏松效果。 ORCID: 0000-0002-9167-5286(赖丽金) 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Effect of apigenin on the osteoporosis in ovariectomized rats and its dose

BACKGROUND:Apigenin has been shown to hold the effects of antivirus,anti-inflammation,anti-oxidation and tranquilizer and sedative.OBJECTIVE:To study the effect of different doses of apigenin on osteoporosis in rats and to explore the underlying mechanism.METHODS:The study was approved by the Laboratory Animal Ethical Committee of Southern Medical University.Forty-two adult male Sprague-Dawley rats were selected,and the rat models of osteoporosis were established by ovariectomy.The rats were divided into seven groups(n=6/group):the sham operation group,the control group,the positive control group,and the 20,40,and 60,and the 80 mg/kg apigenin groups according to the dose of apigenin.The sham operation group did not receive the removal of the ovaries.The positive control group was supplemented with diethylstilbestrol(0.02 mg/kg),vitamin D and calcium daily.The control group was given the subcutaneous injection of same volume of purified water.The apigenin groups were given the subcutaneous injection of various doses of apigenin,respectively,once daily,for 8 weeks.The femoral bone mineral density and serum levels of calcium,phosphorus,bone alkaline phosphatase,amino-terminal propeptide of type I procollagen,C-terminal telopeptide of type I collagen were measured at 4 and 8 weeks after intervention,respectively.RESULTS AND CONCLUSION:(1)Compared with the control group,when the dose of apigenin was 40,60 and 80 mg/kg,the bone mineral density,and serum levels of calcium and phosphorus were increased significantly at 4 and 8 weeks(P<0.05),and the levels of amino-terminal propeptide of type I procollagen,C-terminal telopeptide of type I collagen and bone alkaline phosphatase were decreased significantly(P<0.05).(2)Compared with the positive control group,when the dose of apigenin was 60 and 80 mg/kg,the bone mineral density,serum levels of calcium and phosphorus,the levels of amino-terminal propeptide of type I procollagen,C-terminal telopeptide of type I collagen and bone alkaline phosphatase showed no significant difference at 4 and 8 weeks(P>0.05).When the dose of apigenin was 20 and 40 mg/kg,compared with the positive control group,the bone mineral density,and serum levels of calcium and phosphorus were decreased significantly at 4 and 8 weeks(P<0.05),and the levels of amino-terminal propeptide of type I procollagen,C-terminal telopeptide of type I collagen and bone alkaline phosphatase were increased significantly(P<0.05).(3)Compared with the sham operation group,in the control group,the bone mineral density,and serum levels of calcium and phosphorus were decreased significantly at 4 and 8 weeks(P<0.05),and the levels of amino-terminal propeptide of type I procollagen,C-terminal telopeptide of type I collagen and bone alkaline phosphatase were increased significantly(P<0.05).(4)These results suggest that it is indeed effective to establish a rat osteoporosis model by ovariectomy.The therapeutic effect of apigenin on osteoporosis is dose-related,and a certain dose of apigenin has an anti-osteoporosis effect.