本文關鍵詞： 巴戟天 骨代謝 利塞膦酸鈉 糖皮質(zhì)激素性骨質(zhì)疏松 預防　出處：《北京中醫(yī)藥大學》2017年碩士論文　論文類型：學位論文

【摘要】：糖皮質(zhì)激素性骨質(zhì)疏松(GIOP)是大劑量或長期小劑量應用糖皮質(zhì)激素后出現(xiàn)的副作用,主要表現(xiàn)為骨微結構破壞,骨量減少,骨密度降低,骨強度下降,易出現(xiàn)骨折為特征的一種全身性骨代謝疾病。目前有調(diào)查統(tǒng)計出糖皮質(zhì)激素性骨質(zhì)疏松的發(fā)病率有逐年升高的趨勢,其發(fā)病率高居繼發(fā)性骨質(zhì)疏松的第三位。因此,有效防治糖皮質(zhì)激素性骨質(zhì)疏松是目前使用糖皮質(zhì)激素的最大挑戰(zhàn),GI0P的研究涉及多個學科,如風濕免疫科,血液科,腎病科,骨科等相關學科,也是目前醫(yī)學界大家都在探究的熱點研究。各種西醫(yī)的預防能起到一定的預防作用,但是在使用西藥預防GI0P的過程中出現(xiàn)了很多問題,副作用,經(jīng)濟代價,安全性等受到患者的不滿意。目前,中醫(yī)藥的發(fā)展越來越顯示出了自身的優(yōu)越性,從"腎藏精生髓主骨""補腎亦即補骨"的理論出發(fā),結合目前對于巴戟天的研究進展及導師的研究方向,本實驗選用補腎中藥——巴戟天來預防糖皮質(zhì)激素性骨質(zhì)疏松,并聯(lián)合利塞膦酸鈉來共同預防,探究是否巴戟天具有抗骨質(zhì)疏松的作用;巴戟天和利塞膦酸鈉相比,巴戟天預防GI0P是否具有優(yōu)越性;巴戟天和利塞膦酸鈉連用預防GI0P,是否具有協(xié)同作用;同時,巴戟天能否降低西藥的副作用。本實驗的研究有助于為臨床預防或治療GI0P提供有力的理論依據(jù)。一、研究目的探究巴戟天預防GI0P的作用;巴戟天和利塞膦酸鈉相比,巴戟天預防GI0P是否具有優(yōu)越性;巴戟天和利塞膦酸鈉連用預防GI0P,是否具有協(xié)同作用;同時,巴戟天能否降低西藥的副作用。最終,能否驗證"腎藏精生髓主骨" "補腎亦即補骨"等中醫(yī)藥理論的合理性和科學性。二、研究方法采用動物實驗研究的方法,將60只大鼠隨機分為空白對照組A、模型組B、中藥組C、西藥組D、中西藥組E,每組12只;除A組外,其余4組(B、C、D、E組)于第一周起給大鼠后大腿部肌肉注射地塞米松(DXM)2.5mg · kg-1/次,2次/周,連續(xù)造模13周,誘導建立糖皮質(zhì)激素性骨質(zhì)疏松大鼠模型,同時,第一周起,A、B均組給于蒸餾水灌胃;C組給與濃度為1g生藥/ml、5.Og/kg的巴戟天水煎液灌胃;D組給于1mg/kg的利塞膦酸鈉懸濁液灌胃;E組聯(lián)合給予1g生藥/ml的水煎劑,5.Og/kg的巴戟天和1mg/kg的利塞膦酸鈉懸濁液干預,每天一次,連續(xù)造模13周,本實驗組內(nèi)采用單因素方差分析(one-wayANOVA),組間差異用LSD法,通過對大鼠體重的分析,各組大鼠血清ALP、Ga、P、BGP、CT、E2的分析并得出結論,同時,結合micro-CT的圖像分析,比較說明模型組的造模情況及干預組的療效差異。三、研究結果1、糖皮質(zhì)激素性骨質(zhì)疏松的模型建立用糖皮質(zhì)激素連續(xù)造模13周后,比較骨生化指標,空白對照A組VS模型B組:ALP(63.94±8.15U/L,51.25±6.13U/L),B 組較 A 組明顯下降,存在顯著差異(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),鈣、磷在 A、B 組間未見顯著差異(P＞0.05);BGP(3.74±0.40ng/ml,3.08±0.32ng/ml),B組較 A 組明顯下降,存在顯著差異(P＞0.05);CT(84.13±8.83pg/ml,72.63±12.15pg/ml),B 組較 A 組明顯下降,存在顯著差異(P＞0.05);E2(73.01±8.11pg/ml,51.76±11.47pg/ml),B組較A組明顯下降,存在顯著差異(P＜0.05)。同時,左股骨、腰3椎體影像學比較也存在顯著差異,B組表現(xiàn)出明顯的骨空洞,骨微結構破壞。總之,通過比較分析模型組和空白對照組的骨生化指標和骨微觀結構,最終確定GIOP造模成功。2、巴戟天聯(lián)合利塞膦酸鈉對GIOP的預防作用(1)體重的變化:實驗第4周開始,五組大鼠的體重增長開始出現(xiàn)顯著性差異(P=0.0000.05),A 組較 B、C、D、E 組大鼠體重較顯著升高(P=0.000、0.001、0.000、0.0000.05);B組較其余四組明顯降低,存在顯著差異(P=0.000、0003、0.035、0.0370.05);C與 D、E 組比較未見差異(P=0.323、0.3130.05)。(2)骨生化指標的變化:A、B、C、D、E五組之間的ALP、BGP、CT、E2之間存在顯著差異(F=23.823,9.184,8.005,32.939;P=0.000,0.000,0.000,0.000);B組的 ALP、BGP、CT、E2 均低于 A 組(P=0.001,0.002,0.014,0.000);C 組的 ALP、BGP、CT、E2 均高于 A 組(P=0.000,0.011,0.004,0.000);A 組和 D、E 組的 ALP、BGP、CT、E2 未見明顯差異(Pd=0.566,0.328,0.661,0.305;Pe=0.396,0.572,0.570,0.956);五組間Ga、P未見明顯差異(PGa= 0.207;Pp=0.407)。(3)骨密度的變化:A、B、C、D、E五組之間的左股骨和腰3椎體的骨密度之間存在顯著差異(F=8.996,9.260;P=0.000,0.000);60只大鼠的左股骨和腰3椎體之間存在顯著差異(F=10.641;P=0.001)。(4)骨影像學變化:模型B組與其余四組之間的骨影像學提示:骨微結構存在顯著差異。A、C、D、E組比較未見明顯的影像學差異。四、研究結論(1)地塞米松能成功建立GIOP模型,但是具體造模成功的時間和其他研究存在一定的時間性差異。(2)單味中藥巴戟天可以預防GIOP的發(fā)生,其預防GIOP作用和利塞膦酸鈉的作用相近;中西藥聯(lián)合未見明顯的協(xié)同作用;但是,有中藥巴戟天參與干預的組,其副作用相對少,大鼠體重增長較快。(3)證明了"腎藏精生髓主骨""補腎亦即補骨"理論的合理性和科學性。
[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，

本文編號：1499319