CN116808086A - 黄蜀葵花在制备治疗银屑病的药物中的应用 - Google Patents
黄蜀葵花在制备治疗银屑病的药物中的应用 Download PDFInfo
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Abstract
本发明涉及中医药技术领域，具体为一种黄蜀葵花在制备治疗银屑病的药物中的应用。本发明经药理试验发现，黄蜀葵花可改善咪喹莫特诱导的银屑病样小鼠皮损组织病理形态，降低其表皮厚度，减少角质形成细胞异常增殖，减少CD3+T细胞数量，具有改善银屑病样皮损的作用，可以用于制备治疗银屑病的药物。本发明构建了咪喹莫特诱导的银屑病样小鼠模型，从宏观皮损到微观病理，探究了黄蜀葵花对小鼠银屑病样皮损的改善作用，既能为银屑病治疗提供新的潜在药物，又可开拓黄蜀葵花新的医疗用途及应用领域，具有重要的临床及科研意义。
Description
技术领域
本发明涉及中医药技术领域，特别是涉及一种黄蜀葵花在制备治疗银屑病的药物中的应用。
背景技术
银屑病是一种慢性炎症性疾病，以皮肤红斑、鳞屑、浸润肥厚为主要表现，其组织病理学特征包括表皮角质细胞过度增殖，角化过度伴角化不全，棘层肥厚，表皮嵴延长，真皮T淋巴细胞、中性粒细胞浸润等。世界范围内银屑病成人患病率为0.51％-11.43％，儿童患病率为0％-1.37％，本病病情顽固、反复难愈，严重影响患者身心健康和生活质量。银屑病发病机制涉及遗传、免疫、感染、环境等众多因素，目前认为T细胞，尤其是Th细胞介导的免疫反应是银屑病发病机制的核心。因此，控制炎性反应和调节免疫功能对治疗银屑病具有重要的临床意义。
黄蜀葵花(abelmoschi corolla,AC)为锦葵科植物黄蜀葵Abelmoschus Manihot(L.)Medic.的干燥花冠。研究表明，其主要药理活性成分为金丝桃苷、异槲皮素、杨梅素、槲皮素、芦丁等，具有抗炎、免疫调节、抗氧化、抗肿瘤、抗纤维化等作用。黄蜀葵花多用于治疗糖尿病肾病、IgA肾病、慢性肾小球肾炎等肾脏疾病，相关研究亦大多围绕肾脏疾病展开。而有关黄蜀葵花治疗银屑病的临床及基础研究，目前尚未有报道。
发明内容
本发明目的是提供一种黄蜀葵花在制备治疗银屑病的药物中的应用。
具体而言，本申请提供了如下技术方案：
黄蜀葵花可用于制备治疗银屑病的药物：本发明经药理试验发现，黄蜀葵花可改善咪喹莫特诱导的银屑病样小鼠皮损组织病理形态，降低其表皮厚度，减少角质形成细胞异常增殖，减少CD3+T细胞数量，具有改善银屑病样皮损的作用，可以用于制备治疗银屑病的药物。
一种银屑病样小鼠模型构建方法：小鼠适应性饲养一周后，依据随机数字表法，将小鼠随机分为正常对照组、模型组、阳性药组、高剂量黄蜀葵花组、中剂量黄蜀葵花组和低剂量黄蜀葵花组，每组6只；
小鼠腹腔注射阿佛丁进行麻醉，对背部2cm×3cm区域去毛，备皮后单笼饲养；空白组小鼠背部备皮区域内每日涂抹凡士林62.5mg，其余各组小鼠每日于背部备皮区域内涂抹等量5％咪喹莫特，每日1次，连续5天；用药小鼠皮肤出现红斑、鳞屑、浸润性银屑病样皮损，并每日逐渐加重，造模成功。
其中，所述小鼠为C57BL/6J雄性小鼠，6～8周龄，体重18～22g。
其中，造模同时灌胃给药，抹药前先进行灌胃，每日1次，每只0.2mL，连续5天；正常对照组和模型组给予纯水，阳性药组给予甲氨蝶呤水溶液，黄蜀葵花各剂量组分别给予相应黄蜀葵花水溶液，分别为3.075g/kg、6.15g/kg、12.3g/kg。
与现有技术相比，本发明黄蜀葵花在制备治疗银屑病的药物中的应用至少具有以下有益效果：
本发明构建了咪喹莫特诱导的银屑病样小鼠模型，从宏观皮损到微观病理，探究了黄蜀葵花对小鼠银屑病样皮损的改善作用，既能为银屑病治疗提供新的潜在药物，又可开拓黄蜀葵花新的医疗用途及应用领域，具有重要的临床及科研意义。
下面结合附图对本发明黄蜀葵花在制备治疗银屑病的药物中的应用作进一步说明。
附图说明
图1为各组小鼠第6天皮损表现。
图2为各组小鼠PASI评分
图3为各组小鼠体质量及脾指数比较 ***P<0.001vs C group,###P<0.001vs M group。
图4(a)和图4(b)为各组小鼠皮损病理改变及表皮厚度比较 ***P<0.001vs C group,###P<0.001vs M group。
图5(a)和图5(b)为各组小鼠皮损Ki67的表达 ***P<0.001vs Cgroup,###P<0.001vs M group。
图6(a)和图6(b)为各组小鼠皮损CD3+T细胞的表达 ***P<0.001vs Cgroup,###P<0.001vs M group。
具体实施方式
一、实验材料
1.动物
36只C57BL/6J雄性小鼠，6～8周龄，体重18～22g，由斯贝福(北京)生物技术有限公司提供，动物许可证号为SCXK(京)2019-0010。饲养于北京市中医药研究所SPF级动物饲养间。室温20℃-26℃，相对湿度40％-70％，昼夜明暗交替时间12h/12h，所有动物均自由采食灭菌饲料、饮用灭菌水。动物实验获得北京市中医药研究所动物伦理委员会批准。
2.药物与试剂
AC购自苏中药业集团股份有限公司；5％咪喹莫特乳膏购自四川明欣药业有限责任公司；甲氨蝶呤(methotrexate,MTX)购自上海上药信谊药厂有限公司；兔来源抗Ki-67、CD3抗体购自英国abcam公司；柠檬酸盐抗原修复缓冲液、封闭用羊血清、通用二步法检测试剂盒(兔增强聚合物法检测系统)、DAB显色液、荧光封片剂(含DAPI)购自北京中杉金桥生物技术有限公司；驴抗兔488荧光二抗购自美国Jackson ImmunoResearch公司。
3.实验仪器
组织脱水机、石蜡包埋机、全自动轮转式切片机、烤片机、HE全自动染色仪购自德国Leica，型号分别为ASP6025、EG1150HC、RM2255、HI1220、AUTOSTAINER XL；全自动切片扫描仪及Image Scope图像分析系统购自德国Leica，型号Asperio CS2；正置荧光显微镜及ZEN图像分析系统购自德国Zeiss，型号Axio Imager M2。
二、实验方法
1.实验分组、造模及给药
小鼠适应性饲养一周后，依据随机数字表法，将小鼠随机分为正常对照(control,C)组、模型(model,M)组、阳性药(MTX)组、高剂量AC(high-dose AC,ACH)组，中剂量AC(middle-dose AC,ACM)组，低剂量AC(low-dose AC,ACL)组，每组6只。
采用经典的咪喹莫特诱导的银屑病样小鼠模型。小鼠腹腔注射阿佛丁(0.2mL/10g)进行麻醉，对背部2cm×3cm区域去毛，备皮后单笼饲养。空白组小鼠背部备皮区域内每日涂抹凡士林62.5mg，其余各组小鼠每日于背部备皮区域内涂抹等量5％咪喹莫特，每日1次，连续5天。用药小鼠皮肤出现红斑、鳞屑、浸润性银屑病样皮损，并每日逐渐加重，提示造模成功。
造模同时灌胃给药，抹药前先进行灌胃，每日1次，每只0.2mL，连续5天。C组和M组给予纯水，MTX组给予MTX溶液(1mg/kg，纯水溶解)，AC各剂量组分别给予相应AC水溶液，分别为3.075g/kg、6.15g/kg、12.3g/kg。
2.标本采集
实验第6天进行取材，小鼠称重，阿佛丁麻醉后，眼眶静脉丛取血，3000r/min离心15min取血清备用。处死后快速取小鼠背部皮损组织、脾脏，并称取脾脏质量。
3.观察指标及检测方法
(1)小鼠银屑病样皮损表现及疾病严重程度指数(PASI)评分
每日观察小鼠皮损动态变化并拍照记录，根据PASI评分标准，按0～4分对红斑、鳞屑、浸润3项进行评分。其中0分＝无，皮损表面无可见鳞屑和红斑，与正常皮肤平齐；1分＝轻微，皮损覆有散在细碎鳞屑，皮肤淡红色，皮损轻微高于正常皮肤；2分＝中度，大部分皮损覆有鳞屑，呈片状，有隆起或斑块，呈红色；3分＝重度，全部皮损覆有较厚鳞屑，皮损肥厚，有明显隆起和深红色斑块；4分＝极严重，皮肤全部为皮损表现。3项评分相加为总分，绘制PASI评分趋势图。
(2)小鼠体重及脾指数
根据小鼠体质量与脾脏质量，计算脾指数，脾指数＝脾脏质量(mg)/体质量(g)×10。
(3)苏木精-伊红(hematoxylin-eosin,HE)染色观察小鼠皮损组织形态学改变
背部皮损组织于10％甲醛溶液固定，经脱水、石蜡包埋后切片，厚度为5μm，二甲苯脱蜡、梯度乙醇水化，苏木素染色3分钟，自来水冲洗，纯水洗1分钟，返蓝液洗30分钟，纯水洗1分钟，伊红染色30分钟，梯度乙醇脱水，二甲苯透明，中性树胶封片。在正置光学显微镜下观察各组小鼠皮肤组织结构和炎性细胞浸润情况，每张切片随机选择5个视野拍照，每个视野采用Image Scope软件随机测量5个表皮厚度，取平均值。
(4)免疫荧光法检测小鼠皮损组织Ki-67的表达
背部皮肤于10％甲醛溶液固定48小时，常规脱水，石蜡包埋，切片机切片(5μm)。二甲苯中脱蜡，梯度乙醇水化，纯水泡洗10分钟，柠檬酸盐100℃水浴抗原修复20分钟，于组织上滴加内源性过氧化物酶阻断剂10分钟，滴加封闭用山羊血清37℃孵育30分钟，甩干血清，滴加Ki-67一抗(1:300)，4℃湿盒过夜(18小时)。避光滴加驴抗兔488荧光二抗(1:1000)，37℃避光孵育1小时，用荧光封片剂避光封片。于正置荧光显微镜下观察，每个组织采用ZEN软件随机选取5个视野拍照，对绿色阳性点计数，求取平均值。
(5)免疫组化法检测小鼠皮损组织CD3+T细胞浸润情况
背部皮肤于10％甲醛溶液固定48小时，常规脱水，石蜡包埋，切片机切片(5μm)。二甲苯中脱蜡，梯度乙醇水化，纯水泡洗10分钟，柠檬酸盐100℃水浴抗原修复20分钟，于组织上滴加内源性过氧化物酶阻断剂10分钟，滴加封闭用山羊血清37℃孵育30分钟，甩干血清，滴加CD3一抗(1:60)，4℃湿盒过夜(18小时)。滴加增强酶标山羊抗兔IgG聚合物，37℃孵育1小时，DAB避光显色30秒左右，纯水泡洗10分钟，梯度乙醇脱水，二甲苯透明，中性树胶封片。使用全自动切片扫描仪进行扫描，每个组织采用Image Scope软件随机选取5个视野，对深染褐色的阳性点计数，求取平均值。
4.统计学处理
使用SPSS 20.0和GraphPad Prism 9.0软件对数据进行分析处理，数据以均值±标准差 表示。多组间计量资料比较，若符合正态分布且方差齐，则采用单因素方差分析；若多组间比较有差异，采用LSD法进行两两比较；若不符合正态分布或方差不齐，则采用秩和检验；P＜0.05表示有统计学差异。
三、实验结果
1.AC改善银屑病样小鼠皮损表现
C组小鼠背部皮肤光滑平整、呈粉色，实验期间无明显改变。M组小鼠造模2天后皮肤出现银屑病样皮损，如红斑、鳞屑、浸润增厚，且随时间进展逐渐加重，面积逐渐增大，PASI各项评分及总分均明显高于空白组，提示造模成功。AC各剂量组与M组相比，皮肤红斑、鳞屑、浸润增厚情况均有所减轻，与MTX组皮损相似，且各组PASI评分呈现相同趋势，提示AC可改善银屑病样小鼠皮损表现，见图1-2。
2.各组小鼠体质量及脾指数比较
造模给药第7天，相较于空白组，其余5组小鼠体质量均有明显下降(P<0.001)；各用药组与M组相比，体重略有上升，但无统计学差异(P>0.05)。脾指数可用于评估脾脏免疫功能强弱，M组较C组脾指数明显上升(P<0.001)；与M组相比，MTX组脾指数明显下降(P<0.001)，AC各剂量组略有下降，但无统计学意义(P>0.05)，见图3。
3.AC减少银屑病样小鼠表皮厚度
C组小鼠皮肤组织结构完整，表皮层薄，无炎性细胞浸润。相较于C组，M组小鼠表皮厚度明显增加(P＜0.001)，棘层肥厚，表皮嵴延长，伴角化过度、角化不全，炎性细胞浸润明显，病理表现与银屑病类似。与模型组比较，各用药组表皮厚度均显著减少(P＜0.001)，角化过度和角化不全减轻，炎性细胞浸润减少，提示AC可减少银屑病样小鼠表皮厚度、改善其组织病理形态，见图4(a)和图4(b)。
4.AC抑制银屑病样小鼠角质形成细胞过度增殖
Ki67为细胞核内分裂增殖相关蛋白，可反映细胞增殖活性。结果显示，C组仅在表皮基底层存在少量Ki67+细胞；相较于C组，M组Ki67+细胞数量明显增加(P＜0.001)，分布于基底层、棘层，呈多层分布；与M组比较，AC各剂量组与MTX组Ki67+细胞数量显著减少(P＜0.001)，于基底层单层分布，提示AC可有效抑制银屑病样小鼠角质形成细胞过度增殖，见图5(a)和图5(b)。
5.AC减少银屑病样小鼠皮损CD3+T细胞数量
CD3标记T淋巴细胞，主要表达于真皮层。结果显示，C组CD3+T细胞数量较少；相较于C组，M组真皮层中CD3+T细胞数量显著增多(P＜0.001)；与M组比较，AC各剂量组与MTX组CD3+T细胞数均有明显减少(P＜0.001)，提示AC可减少银屑病样小鼠皮损CD3+T细胞数量、减轻炎性细胞浸润，见图6(a)和图6(b)。
通过以上药理试验发现，黄蜀葵花可改善咪喹莫特诱导的银屑病样小鼠皮损组织病理形态，降低其表皮厚度，减少角质形成细胞异常增殖，减少CD3+T细胞数量，具有改善银屑病样皮损的作用，既能为银屑病治疗提供新的潜在药物，又可开拓黄蜀葵花新的医疗用途及应用领域，具有重要的临床及科研价值。
以上所述的实施例仅仅是对本发明的优选实施方式进行描述，并非对本发明的范围进行限定，在不脱离本发明设计精神的前提下，本领域普通技术人员对本发明的技术方案作出的各种变形和改进，均应落入本发明权利要求书确定的保护范围内。
Claims (4)
1.黄蜀葵花在制备治疗银屑病的药物中的应用。
2.根据权利要求1所述黄蜀葵花在制备治疗银屑病的药物中的应用，其特征在于：包括银屑病样小鼠模型构建方法，具体为：小鼠适应性饲养一周后，依据随机数字表法，将小鼠随机分为正常对照组、模型组、阳性药组、高剂量黄蜀葵花组、中剂量黄蜀葵花组和低剂量黄蜀葵花组，每组6只；
小鼠腹腔注射阿佛丁进行麻醉，对背部2cm×3cm区域去毛，备皮后单笼饲养；空白组小鼠背部备皮区域内每日涂抹凡士林62.5mg，其余各组小鼠每日于背部备皮区域内涂抹等量5％咪喹莫特，每日1次，连续5天；用药小鼠皮肤出现红斑、鳞屑、浸润性银屑病样皮损，并每日逐渐加重，造模成功。
3.根据权利要求2所述的黄蜀葵花在制备治疗银屑病的药物中的应用，其特征在于：所述小鼠为C57BL/6J雄性小鼠，6～8周龄，体重18～22g。
4.根据权利要求3所述的黄蜀葵花在制备治疗银屑病的药物中的应用，其特征在于：造模同时灌胃给药，抹药前先进行灌胃，每日1次，每只0.2mL，连续5天；正常对照组和模型组给予纯水，阳性药组给予甲氨蝶呤水溶液，黄蜀葵花各剂量组分别给予相应黄蜀葵花水溶液，分别为3.075g/kg、6.15g/kg、12.3g/kg。
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| CN109331032A (zh) * | 2018-11-09 | 2019-02-15 | 中国人民解放军陆军特色医学中心 | 金丝桃苷在制备治疗瘙痒性皮肤病的药物中的应用 |
| CN114558003A (zh) * | 2022-03-11 | 2022-05-31 | 中国药科大学 | 汉黄芩素衍生物gl-v9在制备银屑病治疗药物中的应用 |
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| CN109331032A (zh) * | 2018-11-09 | 2019-02-15 | 中国人民解放军陆军特色医学中心 | 金丝桃苷在制备治疗瘙痒性皮肤病的药物中的应用 |
| CN114558003A (zh) * | 2022-03-11 | 2022-05-31 | 中国药科大学 | 汉黄芩素衍生物gl-v9在制备银屑病治疗药物中的应用 |
Non-Patent Citations (4)
| Title |
|---|
| 周兢兢: "基于网络药理学和分子对接技术探析除湿解毒饮治疗银屑病的作用机制", 中医临床研究, vol. 15, no. 1, 10 January 2023 (2023-01-10), pages 14 - 21 * |
| 张蕊: "闵仲生从脾论治寻常型银屑病经验", 山东中医药大学学报, vol. 42, no. 04, 28 June 2018 (2018-06-28), pages 330 - 331 * |
| 张颖: "李斌教授治疗银屑病血燥证经验探微", 上海医药, vol. 43, no. 13, 10 July 2022 (2022-07-10), pages 40 - 42 * |
| 陈淑娴: "含黄蜀葵花外用制剂的研究进展", 上海医药, vol. 38, no. 05, 10 March 2017 (2017-03-10), pages 75 - 78 * |
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