巴戟天联合利塞膦酸钠预防糖皮质激素诱导大鼠骨质疏松的实验研究

发布时间：2018-02-10 01:20

  本文关键词： 巴戟天 骨代谢 利塞膦酸钠 糖皮质激素性骨质疏松 预防　出处：《北京中医药大学》2017年硕士论文　论文类型：学位论文

【摘要】：糖皮质激素性骨质疏松(GIOP)是大剂量或长期小剂量应用糖皮质激素后出现的副作用,主要表现为骨微结构破坏,骨量减少,骨密度降低,骨强度下降,易出现骨折为特征的一种全身性骨代谢疾病。目前有调查统计出糖皮质激素性骨质疏松的发病率有逐年升高的趋势,其发病率高居继发性骨质疏松的第三位。因此,有效防治糖皮质激素性骨质疏松是目前使用糖皮质激素的最大挑战,GI0P的研究涉及多个学科,如风湿免疫科,血液科,肾病科,骨科等相关学科,也是目前医学界大家都在探究的热点研究。各种西医的预防能起到一定的预防作用,但是在使用西药预防GI0P的过程中出现了很多问题,副作用,经济代价,安全性等受到患者的不满意。目前,中医药的发展越来越显示出了自身的优越性,从"肾藏精生髓主骨""补肾亦即补骨"的理论出发,结合目前对于巴戟天的研究进展及导师的研究方向,本实验选用补肾中药——巴戟天来预防糖皮质激素性骨质疏松,并联合利塞膦酸钠来共同预防,探究是否巴戟天具有抗骨质疏松的作用;巴戟天和利塞膦酸钠相比,巴戟天预防GI0P是否具有优越性;巴戟天和利塞膦酸钠连用预防GI0P,是否具有协同作用;同时,巴戟天能否降低西药的副作用。本实验的研究有助于为临床预防或治疗GI0P提供有力的理论依据。一、研究目的探究巴戟天预防GI0P的作用;巴戟天和利塞膦酸钠相比,巴戟天预防GI0P是否具有优越性;巴戟天和利塞膦酸钠连用预防GI0P,是否具有协同作用;同时,巴戟天能否降低西药的副作用。最终,能否验证"肾藏精生髓主骨" "补肾亦即补骨"等中医药理论的合理性和科学性。二、研究方法采用动物实验研究的方法,将60只大鼠随机分为空白对照组A、模型组B、中药组C、西药组D、中西药组E,每组12只;除A组外,其余4组(B、C、D、E组)于第一周起给大鼠后大腿部肌肉注射地塞米松(DXM)2.5mg · kg-1/次,2次/周,连续造模13周,诱导建立糖皮质激素性骨质疏松大鼠模型,同时,第一周起,A、B均组给于蒸馏水灌胃;C组给与浓度为1g生药/ml、5.Og/kg的巴戟天水煎液灌胃;D组给于1mg/kg的利塞膦酸钠悬浊液灌胃;E组联合给予1g生药/ml的水煎剂,5.Og/kg的巴戟天和1mg/kg的利塞膦酸钠悬浊液干预,每天一次,连续造模13周,本实验组内采用单因素方差分析(one-wayANOVA),组间差异用LSD法,通过对大鼠体重的分析,各组大鼠血清ALP、Ga、P、BGP、CT、E2的分析并得出结论,同时,结合micro-CT的图像分析,比较说明模型组的造模情况及干预组的疗效差异。三、研究结果1、糖皮质激素性骨质疏松的模型建立用糖皮质激素连续造模13周后,比较骨生化指标,空白对照A组VS模型B组:ALP(63.94±8.15U/L,51.25±6.13U/L),B 组较 A 组明显下降,存在显著差异(P＜0.05);Ga(2.46±0.11mmol/L,2.51±0.09mmol/L),P(1.49±0.08mmol/L,1.50±0.06mmol/L),钙、磷在 A、B 组间未见显著差异(P＞0.05);BGP(3.74±0.40ng/ml,3.08±0.32ng/ml),B组较 A 组明显下降,存在显著差异(P＞0.05);CT(84.13±8.83pg/ml,72.63±12.15pg/ml),B 组较 A 组明显下降,存在显著差异(P＞0.05);E2(73.01±8.11pg/ml,51.76±11.47pg/ml),B组较A组明显下降,存在显著差异(P＜0.05)。同时,左股骨、腰3椎体影像学比较也存在显著差异,B组表现出明显的骨空洞,骨微结构破坏。总之,通过比较分析模型组和空白对照组的骨生化指标和骨微观结构,最终确定GIOP造模成功。2、巴戟天联合利塞膦酸钠对GIOP的预防作用(1)体重的变化:实验第4周开始,五组大鼠的体重增长开始出现显著性差异(P=0.0000.05),A 组较 B、C、D、E 组大鼠体重较显著升高(P=0.000、0.001、0.000、0.0000.05);B组较其余四组明显降低,存在显著差异(P=0.000、0003、0.035、0.0370.05);C与 D、E 组比较未见差异(P=0.323、0.3130.05)。(2)骨生化指标的变化:A、B、C、D、E五组之间的ALP、BGP、CT、E2之间存在显著差异(F=23.823,9.184,8.005,32.939;P=0.000,0.000,0.000,0.000);B组的 ALP、BGP、CT、E2 均低于 A 组(P=0.001,0.002,0.014,0.000);C 组的 ALP、BGP、CT、E2 均高于 A 组(P=0.000,0.011,0.004,0.000);A 组和 D、E 组的 ALP、BGP、CT、E2 未见明显差异(Pd=0.566,0.328,0.661,0.305;Pe=0.396,0.572,0.570,0.956);五组间Ga、P未见明显差异(PGa= 0.207;Pp=0.407)。(3)骨密度的变化:A、B、C、D、E五组之间的左股骨和腰3椎体的骨密度之间存在显著差异(F=8.996,9.260;P=0.000,0.000);60只大鼠的左股骨和腰3椎体之间存在显著差异(F=10.641;P=0.001)。(4)骨影像学变化:模型B组与其余四组之间的骨影像学提示:骨微结构存在显著差异。A、C、D、E组比较未见明显的影像学差异。四、研究结论(1)地塞米松能成功建立GIOP模型,但是具体造模成功的时间和其他研究存在一定的时间性差异。(2)单味中药巴戟天可以预防GIOP的发生,其预防GIOP作用和利塞膦酸钠的作用相近;中西药联合未见明显的协同作用;但是,有中药巴戟天参与干预的组,其副作用相对少,大鼠体重增长较快。(3)证明了"肾藏精生髓主骨""补肾亦即补骨"理论的合理性和科学性。
[Abstract]:Glucocorticoid induced osteoporosis (GIOP) is the side effects of high doses or long-term low-dose glucocorticoids, reduce the main performance for the destruction of bone microstructure of bone mass, decreased bone density, bone strength decrease, easy fracture is a systemic metabolic bone disease characterized. There are statistical the pathogenesis of glucocorticoid induced osteoporosis rate is increasing year by year, the incidence of osteoporosis in third. Therefore, the effective prevention and treatment of glucocorticoid induced osteoporosis is the biggest challenge of using glucocorticoid, GI0P's research involves many disciplines, such as rheumatism immunology, Department of Hematology, Department of nephropathy. Department of orthopedics and other related disciplines, is currently the medical profession for everyone in the hot research. The prevention of Western medicine can play a preventive role, but there are many problems in the process of the use of Western medicine in the prevention of GI0P, Side effects, economic costs, safety by the patients satisfied. At present, the development of Chinese medicine more and more shows its advantages, from the "kidney essence" kidney is the main bone marrow "bonestrengthening" theory, combined with the current research progress and direction guide for division of Morinda officinalis in this experiment, Bushen Chinese medicine Morinda - to prevent glucocorticoid induced osteoporosis, and combined risedronate sodium to prevent, investigate whether Morinda has anti osteoporosis effect; compared Morinda officinalis and risedronate, Morinda GI0P prevention and superiority of Morinda officinalis and risedronate; sodium for prevention of GI0P, it has a synergistic effect; at the same time, Bajitian can reduce the side effects of Western medicine. This study is helpful to provide a strong theoretical basis for clinical prevention and treatment of GI0P. The purpose of the study is to explore a GI0P for prevention of Morinda officinalis 鐢，

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