CN103494819A - 喜树碱在类风湿关节炎中的作用 - Google Patents
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Abstract
一种喜树碱在类风湿关节炎中的作用，本发明涉及喜树碱对胶原诱导关节炎模型的免疫抑制功能及其对RA患者外周血单个核细胞免疫调节作用的研究，探讨其在类风湿关节炎治疗中的应用。我们通过实验已证实喜树碱可有效抑制关节炎症，降低骨质破坏程度，有效地缓解RA病情。
Description
技术领域
本研究涉及喜树碱对胶原诱导关节炎(collagen induced arthritis，CIA)模型的免疫抑制功能及其对RA患者外周血单个核细胞(peripheral blood mononuclear cell，PBMC)免疫调节作用的研究，探讨其在类风湿关节炎(rheumatoid arthritis，RA)治疗中的应用。
背景技术
类风湿关节炎(rheumatoid arthritis，RA)是一种自身免疫性疾病，以慢性进行性关节破坏为特征，约占总人口的0.5-1％，也是我国最主要的引起青壮年劳动力丧失的原因之一。其病理特点是关节滑膜组织中大量炎症细胞聚集增生，滑膜细胞和血管增生，增生的滑膜组织向关节软骨面生长并侵蚀关节软骨并分泌多种炎性因子和酶类，引起关节软骨及骨的破坏，最后关节畸形强直、功能障碍，导致残疾。迄今为止，发病原因不明，本病治疗上缺乏有效的药物和手段。目前治疗此类疾病的药物主要为改善病情抗风湿药(DMARDs)，最初作为抗肿瘤药的甲氨喋呤、环磷酰胺等也作为免疫抑制剂治疗自身免疫性疾病，但有较多患者出现不良反应，导致不能耐受而停用。
喜树碱(camptothecin，CPT)是从我国特有的珙桐科植物中提取出来的新型有效的抗肿瘤药物，是迄今唯一的一种拓扑异构酶I的抑制剂。目前已在胃癌、乳腺癌、卵巢癌、等恶性肿瘤的治疗中得到广泛的应用。其抗肿瘤作用机制主要有：(1)阻断肿瘤细胞Topo-I。Topo-I对维持DNA机构和功能以及保证细胞的存活至关重要，并与肿瘤细胞分化、增殖关系密切。(2)CPT可显著抑制组蛋白H1和H3磷酸化，其对肿瘤细胞的致死作用至少部分与其抑制组蛋白H1和H3有关。(3)CPT亦可和Topo-I/单链DNA复合体形成稳定的结合体，抑制Topo-I解旋和再连接功能，诱导DNA不可逆性断裂，启动细胞周期阻滞。
由于RA的病理过程为滑膜细胞和血管增生，类似肿瘤样的表现，因此，肿瘤抑制剂CPT很有可能成为一种新型的治疗RA的药物。我们通过实验已证实CPT可有效抑制关节炎症，降低骨质破坏程度，有效地缓解RA病情。
发明内容
为了深入探讨CPT对RA治疗的作用，我们从大鼠RA模型和RA患者外周血两方面进行了研究。首先，动物实验中，我们对6周龄雌性Lewis大鼠，尾根部皮内免疫bC II建CIA模型，于初次免疫后第14天大鼠出现关节炎，随机分为三组，CPT2mg/kg，每日腹腔注射，MTX阳性对照组1mg/kg，1/周，腹腔注射。同时生理盐水对照组200ul腹腔注射，1/日。连续治疗4周结果显示，与空白对照组相比，2mg/kgCPT治疗后能够明显抑制大鼠的关节炎症，降低骨质破坏程度。
其次，我们通过体外实验进行了CPT刺激前后RA患者PBMC细胞增殖、凋亡及细胞上清的表达水平来研究CPT的免疫抑制作用。不同浓度的CPT对体外培养PBMC的作用，结果显示，CPT作用72小时后，对PBMC增殖有明显抑制作用，且呈现剂量依赖性；药物刺激后可显著诱导细胞凋亡；并能上调TGF-β1的表达，说明CPT具有明显的免疫抑制作用。
附图说明
图1.喜树碱治疗不影响大鼠体重，6周龄雌性Lewis大鼠，尾根部皮内免疫bC II建CIA模型，CPT治疗期间三组大鼠体重呈稳定增长趋势，无明显差异，未观察到腹泻、毛色差等不良反应，治疗第17天以后，体重增长较快说明CPT相对安全，副作用小。
图2.喜树碱治疗明显降低关节炎大鼠的临床评分，CPT治疗28天结束时，CPT治疗组、MTX治疗组及生理盐水对照组关节炎评分分别为0、0.3、5，CPT治疗组及MTX治疗组与对照组相比，关节炎评分明显降低，差异有统计学意义，p＜0.05。
图3.不同浓度CPT、CTX分别刺激后RA的PBMC增殖情况比较，3H掺入法检测不同浓度CPT及CTX对PBMC增殖能力的影响。结果显示，CPT刺激PBMC后CPM值明显减低，且随剂量的增加，抑制作用增强，呈现剂量依赖性，(三种工作浓度的组100ug/ml浓度组、10ug/ml浓度组、1ug/ml CPT浓度组刺激后细胞CPM值分别为1708.57±584.48、3139.14±922.08、4741.33±985.5，三组之间比较差异具有统计学意义P＜0.05)。CTX刺激后细胞CPM值较CPT增高，且差异具有统计学意义。
图4.CPT刺激PBMC72小时后细胞凋亡情况，CPT对RA患者PBMC的凋亡作用的影响：经CPT刺激后细胞凋亡率明显高于PBMC组，且两组相比较，差异具有统计学意义(凋亡率分别为6.8±5.4，30.0±13.1；P=0.047)。同样，PBMC+PHA+CPT组凋亡率高于PBMC+PHA组，两组相比较差异具有统计学意义(凋亡率分别为14.23±3.6，33.6±11.1；P=0.034)。
图5.培养72小时后细胞上清TGF-β1水平的变化，CPT对RA患者PBMC细胞上清中TGF-β1表达水平的影响：结果发现经CPT刺激后细胞上清TGF-β1的表达明显高于PBMC组(1555.93±382.51，986.84±271.00，p＜0.05)；经PHA+CPT共同刺激后的PBMC细胞上清TGF-β1的表达明显高于PHA刺激组，(839.35±585.02，1283.97±198.24，P＝0.052)。
表1.注射生理盐水对照组的大鼠踝关节滑膜组织HE染色显示，大量炎性细胞浸润、聚集；滑膜细胞增生，可达10层以上，排列疏散、紊乱；滑膜下组织血管扩张，数量增多，血管翳形成。而CPT治疗组大鼠踝关节病理学评分明显低于对照组(*，P＜0.01)，而与MTX治疗组相比，病理学评分差异无统计学意义，这些结果表明，CPT可明显抑制CIA的骨质破坏。
表2.CPT治疗组大鼠血清中TNF-α明显下降，但与对照组相比差异无统计学意义，VEGF与 MTX治疗组及对照组接近，IL-1β比对照组下降明显，但无统计学差异。
具体实施方式
实施例1：CPT治疗CIA大鼠
6周龄雌性Lewis大鼠，尾根部皮内免疫bC II建CIA模型，发病鼠共36只，随机分为三组，CPT2mg/kg，每日腹腔注射，MTX阳性对照组1mg/kg，1/周，腹腔注射。同时生理盐水对照组200ul腹腔注射，1/日。连续治疗4周结果显示，治疗期间三组大鼠体重呈稳定增长趋势，无明显差异，见图1。与空白对照组相比，2mg/kgCPT治疗能够明显抑制大鼠的关节炎症，降低骨质破坏程度，明显降低关节炎临床及病理评分，见图2、表1。这说明：CPT对大鼠CIA具有明显的抑制作用。此外，CPT治疗组大鼠血清中致炎性细胞因子的表达明显下降，见表2。
实施例2：不同浓度CPT对PBMC抑制增殖的作用
RA患者PBMC的分离
①无菌抽取患者静脉抗凝血15-20ml，并用PBS缓冲液等体积稀释。②稀释后的血液等体积轻铺于含人淋巴细胞分离液的15ml无菌离心管中，2000rpm，离心20min。③吸取中间层单个核细胞，用PBS液洗涤2次(1500rpm，离心5min)，弃上清。④以含10％FBS的RPMI-1640培养液混匀。
药物对细胞刺激作用分组情况
分组加药：①调整细胞浓度，接种于96孔培养板，每孔铺2-4×105/ml细胞悬液，每孔总体积为200μl。将细胞分为阴性对照组、PHA对照组(PHA工作浓度为2μg/ml)、CPT刺激组(设三个工作浓度梯度1μg/ml、10μg/ml、100μg/ml)、CTX刺激组(工作浓度为1μg/ml)，且每组细胞设3个复孔。37℃、5％CO2培养箱孵育后，72h检测药物对细胞增殖的影响。
将PBMC铺于96孔板内，2-4×105ml/孔，每组细胞均为三复孔。按上述步骤分别对6组细胞培养，其中对药物刺激组和PHA对照组均进行PHA刺激(工作浓度2μg/ml)，结束培养前10小时每孔加入1μCi3H标记的胸腺嘧啶核苷(3H-TdR)，3H掺入法检测药物对PBMC增殖情况的影响。以每分钟脉冲数(CPM)评价6组细胞增殖反应情况，见图3。
实施例3：CPT对PBMC诱导凋亡的作用及对细胞上清的作用
调整细胞浓度，接种于24孔培养板，每孔铺2×106/ml细胞悬液，每孔总体积为1.5ml。将细胞分为阴性对照组、PHA对照组、CPT刺激组(工作浓度为1μg/ml)，培养72h后应用 酶联免疫吸附法(ELISA)法检测细胞上清TGF-β1水平，以及应用Annexin V/PI流式细胞术检测CPT对细胞凋亡的影响。
细胞凋亡的检测：从上述24孔培养板中取出培养的细胞，将其转入流式管中，用PBS洗涤2遍，调整细胞浓度为每管1×106ml，将每只管中加入10μl Annexin V混匀，室温避光15min，洗细胞1遍，后加入5μl的PI，应用流式细胞仪进行细胞凋亡的检测，见图4。
ELISA法检测药物刺激后PBMC上清的TGF-β1分泌水平：按上述方法对24孔培养板中培养72h后留取细胞上清，按照ELISA试剂盒说明书进行检测细胞上清TGF-β1的分泌水平，见图5。
表1喜树碱治疗对大鼠CIA病理学评分的影响
表2喜树碱治疗对大鼠CIA血清学指标的影响
Claims (2)
1.喜树碱在制备类风湿关节炎治疗药物中的应用。
2.权利要求1的喜树碱为一种植物药，从喜树中提取得到。
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Non-Patent Citations (2)
| Title |
|---|
| OTILIA MAY YUE KOO ET AL.: "Actively Targeted Low-Dose Camptothecin as a Safe,Long-Acting,Disease-Modifying Nanomedicine for Rheumatoid Arthritis. Otilia May Yue Koo et al.Pharmaceutical Research.2011.Volume 28,Issue 4,pp776-787", 《PHARMACEUTICAL RESEARCH》 * |
| 吴基良等: "《药理学(第2版)》", 31 January 2012, 科学出版社 * |
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