中国组织工程研究与临床康复
中國組織工程研究與臨床康複
중국조직공정연구여림상강복
JOURNAL OF CLINICAL REHABILITATIVE TISSUE ENGINEERING RESEARCH
2009年
53期
10452-10456
,共5页
背景:根据现有理论及治疗经验,创新性提出自身免疫性疾病时体内细胞变异是永久存在的,且这些变异体细胞是引起自身免疫性疾病的原因或者同时伴有免疫细胞的变异,使用免疫清零耐受诱导新生的免疫系统对变异体细胞产生耐受,即能治愈除干细胞病变以外自身免疫性疾病的假设.目的:拟验证免疫清零驯化治疗免疫性肌炎动物模型的疗效.设计、时间及地点:随机分组、对比观察动物实验,于2008-12/2009-04在南方医院动物实验中心完成.材料:雌性成年新西兰兔1只,体质量4.1 kg;雌性清洁级英格兰短毛豚鼠36只,体质量400～500 g.方法:用新西兰兔肌肉匀浆混合完全弗氏佐剂对豚鼠进行免疫注射制作免疫性肌炎豚鼠模型.造模后,28只豚鼠抽签法随机分为:超大剂量清零驯化组,白消安1 mg/kg,12 h/次,8次,白消安给药结束后腹腔注射环磷酰胺40 mg/kg,1次/d,4次,环磷酰胺给药结束后腹腔注射环孢素A 3 mg/kg,1次/d,持续至动物死亡;环磷酰胺组,腹腔注射环磷酰胺10 mg/kg,1次/d,3次;免疫清零驯化组,白消安0.8 mg/kg, 环磷酰胺30 mg/kg,环孢素A 3 mg/kg,给药次数及方式同超大剂量清零驯化组;对照组为空白对照.主要观察指标:给药前后进行全血细胞检查及生化检测,记录动物给药后生存时间,观察各组肌肉组织病理变化.结果:与对照组比较,其他组免疫后白细胞均明显降低,给药后造血功能逐渐恢复,免疫清零驯化组白细胞计数增高最明显,横纹肌病理检查发现肌肉组织病理改变以骨骼肌多发性炎症为特点.给药后超大剂量免疫清零驯化组及免疫清零驯化组谷草转氨酶、肌酸激酶较给药前明显下降(P < 0.05,P < 0.01),但横纹肌病理检查未见明显改变;环磷酰胺组与对照组谷草转氨酶、肌酸激酶、乳酸脱氢酶均无明显变化.超大剂量清零驯化组动物生存时间最短,环磷酰胺组与对照组无差异,免疫清零驯化组动物生存时间明显优于其他各组.结论:免疫清零驯化治疗免疫性肌炎动物模型有显著疗效,且效果优于超大剂量清零驯化治疗及常规剂量免疫抑制剂治疗.
揹景:根據現有理論及治療經驗,創新性提齣自身免疫性疾病時體內細胞變異是永久存在的,且這些變異體細胞是引起自身免疫性疾病的原因或者同時伴有免疫細胞的變異,使用免疫清零耐受誘導新生的免疫繫統對變異體細胞產生耐受,即能治愈除榦細胞病變以外自身免疫性疾病的假設.目的:擬驗證免疫清零馴化治療免疫性肌炎動物模型的療效.設計、時間及地點:隨機分組、對比觀察動物實驗,于2008-12/2009-04在南方醫院動物實驗中心完成.材料:雌性成年新西蘭兔1隻,體質量4.1 kg;雌性清潔級英格蘭短毛豚鼠36隻,體質量400～500 g.方法:用新西蘭兔肌肉勻漿混閤完全弗氏佐劑對豚鼠進行免疫註射製作免疫性肌炎豚鼠模型.造模後,28隻豚鼠抽籤法隨機分為:超大劑量清零馴化組,白消安1 mg/kg,12 h/次,8次,白消安給藥結束後腹腔註射環燐酰胺40 mg/kg,1次/d,4次,環燐酰胺給藥結束後腹腔註射環孢素A 3 mg/kg,1次/d,持續至動物死亡;環燐酰胺組,腹腔註射環燐酰胺10 mg/kg,1次/d,3次;免疫清零馴化組,白消安0.8 mg/kg, 環燐酰胺30 mg/kg,環孢素A 3 mg/kg,給藥次數及方式同超大劑量清零馴化組;對照組為空白對照.主要觀察指標:給藥前後進行全血細胞檢查及生化檢測,記錄動物給藥後生存時間,觀察各組肌肉組織病理變化.結果:與對照組比較,其他組免疫後白細胞均明顯降低,給藥後造血功能逐漸恢複,免疫清零馴化組白細胞計數增高最明顯,橫紋肌病理檢查髮現肌肉組織病理改變以骨骼肌多髮性炎癥為特點.給藥後超大劑量免疫清零馴化組及免疫清零馴化組穀草轉氨酶、肌痠激酶較給藥前明顯下降(P < 0.05,P < 0.01),但橫紋肌病理檢查未見明顯改變;環燐酰胺組與對照組穀草轉氨酶、肌痠激酶、乳痠脫氫酶均無明顯變化.超大劑量清零馴化組動物生存時間最短,環燐酰胺組與對照組無差異,免疫清零馴化組動物生存時間明顯優于其他各組.結論:免疫清零馴化治療免疫性肌炎動物模型有顯著療效,且效果優于超大劑量清零馴化治療及常規劑量免疫抑製劑治療.
배경:근거현유이론급치료경험,창신성제출자신면역성질병시체내세포변이시영구존재적,차저사변이체세포시인기자신면역성질병적원인혹자동시반유면역세포적변이,사용면역청령내수유도신생적면역계통대변이체세포산생내수,즉능치유제간세포병변이외자신면역성질병적가설.목적:의험증면역청령순화치료면역성기염동물모형적료효.설계、시간급지점:수궤분조、대비관찰동물실험,우2008-12/2009-04재남방의원동물실험중심완성.재료:자성성년신서란토1지,체질량4.1 kg;자성청길급영격란단모돈서36지,체질량400～500 g.방법:용신서란토기육균장혼합완전불씨좌제대돈서진행면역주사제작면역성기염돈서모형.조모후,28지돈서추첨법수궤분위:초대제량청령순화조,백소안1 mg/kg,12 h/차,8차,백소안급약결속후복강주사배린선알40 mg/kg,1차/d,4차,배린선알급약결속후복강주사배포소A 3 mg/kg,1차/d,지속지동물사망;배린선알조,복강주사배린선알10 mg/kg,1차/d,3차;면역청령순화조,백소안0.8 mg/kg, 배린선알30 mg/kg,배포소A 3 mg/kg,급약차수급방식동초대제량청령순화조;대조조위공백대조.주요관찰지표:급약전후진행전혈세포검사급생화검측,기록동물급약후생존시간,관찰각조기육조직병리변화.결과:여대조조비교,기타조면역후백세포균명현강저,급약후조혈공능축점회복,면역청령순화조백세포계수증고최명현,횡문기병리검사발현기육조직병리개변이골격기다발성염증위특점.급약후초대제량면역청령순화조급면역청령순화조곡초전안매、기산격매교급약전명현하강(P < 0.05,P < 0.01),단횡문기병리검사미견명현개변;배린선알조여대조조곡초전안매、기산격매、유산탈경매균무명현변화.초대제량청령순화조동물생존시간최단,배린선알조여대조조무차이,면역청령순화조동물생존시간명현우우기타각조.결론:면역청령순화치료면역성기염동물모형유현저료효,차효과우우초대제량청령순화치료급상규제량면역억제제치료.
BACKGROUND: According to present theories and our clinical experience, immune ablative and tolerance inducing theory is proposed. Immune ablative means to clear out mutate cell clones and without transfusion of hemopoietic stem cells afterwards; intolerance inducing means to induce animal models not to react to mutate somatic cells, which avoids relapse or new occurrence of autoimmune disease. OBJECTIVE: To explore the effects of immune-ablative and tolerance inducing therapy in treating animal model of immune polymyositis (PM). DESIGN, TIME AND SETTING: Randomized, controlled animal experiment was performed at the Animal Experimental Center of Nanfang Hospital from December 2008 to April 2009. MATERIALS: One New Zealand rabbit, female, weighing 4.1 kg and 36 England guinea pigs, female, weighing 400-500 g, were used. METHODS: New Zealand rabbit's muscle tissue homogenate and complete Freund's adjuvant (CFA) were injected into guinea pigs to make PM animal models. The 28 animal models were randomly divided into intense immune-ablative and tolerance inducing group (Busulfan 1 mg/kg, every 12 hours, totally 8 doses; followed by CTX 40 mg/kg per day for 4 days; then cyclosporine A (CsA) 3 mg/kg per day was given till animals were dead); cyclophosphamide (CTX) group: CTX was given, 10 mg/kg per day for 3days; immune-ablative and tolerance inducing group: Busulfan 0.8 mg/kg, CTX 30 mg/kg, CsA 3 mg/kg; the administration time and dose were the same as group 1. Control group was not treated.MAIN OUTCOME MEASURES: Full blood count (FBC) and biochemical index were tested before and after treatment, and surviving time was recorded. In addition, muscle pathological changes were observed.RESULTS: Compared with control group, number of white cells was significantly decreased in the other groups, and hematopoiesis function gradually restored after administration. The number of white cells in the immune-ablative and tolerance inducing group was the most, and striated muscle pathology showed PM. Following administration, the glutamic oxaloacetic transaminase and creatine kinase of intense immune-ablative and tolerance inducing and immune-ablative and tolerance inducing groups were significantly reduced (P < 0.05, P < 0.01), but no obvious striated muscle pathological changes were found. The glutamic oxaloacetic transaminase, lactic dehydrogenase and creatine kinase in the CTX and control groups remained unchanged. Survival time of intense immune-ablative and tolerance inducing group was the shortest among all groups, and there was no significant difference between CTX and control groups. The animals in immune-ablative and tolerance inducing group survived for the longest time. CONCLUSION: Immune-ablative and tolerance inducing therapy has preferable effect on treating animal models of PM, and its prognosis is better than intense immune-ablative and tolerance inducing therapy and regular CTX therapy.
