CN116270870B - 一种治疗膜性肾病的中药组合物及其制备方法 - Google Patents
一种治疗膜性肾病的中药组合物及其制备方法 Download PDFInfo
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- Medicines Containing Plant Substances (AREA)
Abstract
本发明公开了一种治疗膜性肾病的中药组合物及其制备方法,属于中医药技术领域,中药组合物内包括中药原料药,其中,中药原料药由以下重量份的中药材组成:生黄芪10~120份,白术10~60份,枸杞10~60份,杜仲10~60份,蝉蜕5~30份,青风藤10~60份,鬼箭羽10~75份,穿山龙10~75份,败酱草10~60份,金樱子10~75份,车前子10~30份,五味子10~75份,土鳖虫10~30份,当归10~60份。临床试验表明,本发明所提供的中药组合物可较快改善患者症状、减轻蛋白尿,疗效稳定且安全性较高。
Description
技术领域
本发明涉及中医药技术领域,具体涉及一种治疗膜性肾病的中药组合物及其制备方法。
背景技术
膜性肾病以肾小球基底膜上皮细胞下免疫复合物沉积伴基底膜弥漫增厚为特征的一组疾病,病因未明者称为特发性膜性肾病,是成人肾病综合征常见的病理类型之一。目前,膜性肾病的发病率逐年攀升,其病程迁延难愈,已成为原发性肾小球疾病进入终末期肾脏病的主要病因之一。现阶段,对于膜性肾病的主要治疗目标为缓解肾病综合征、减少蛋白尿、保护肾功能,以期延缓疾病进展。对于膜性肾病的治疗,根据其风险分层进行,针对低风险患者多以降压、降尿蛋白、减轻水肿、抗凝、降脂等对症治疗为主;针对中高风险患者在对症治疗的基础上加用免疫抑制剂进行治疗,临床常用的免疫抑制剂主要有钙调磷酸酶抑制剂、糖皮质激素和环磷酰胺。但是,采用免疫抑制剂治疗存在疗效不稳定、副作用大、复发率高等问题。利妥昔单抗是一种人鼠嵌合性单克隆抗体,能特异性地与跨膜抗原CD20结合,目前已成为膜性肾病的一线用药。然而利妥昔单抗价格昂贵,且利妥昔单抗对人体免疫系统损伤较大,因此会增加患者感染的风险。
因此,临床亟需疗效可靠、安全性高的治疗药物。
发明内容
为此,本发明提供一种治疗膜性肾病的中药组合物及其制备方法,以解决现有技术中针对膜性肾病的治疗缺乏疗效佳、副作用小的临床用药问题。
为了实现上述目的,本发明提供如下技术方案:
本发明的第一个目的,提供一种治疗膜性肾病的中药组合物;
本发明的第二个目的,提供上述治疗膜性肾病中药组合物的制备方法;
本发明的第三个目的,是提供上述治疗膜性肾病中药组合物的用途。
为实现第一个目的,本发明所采取的技术方案是:
一种治疗膜性肾病的中药组合物,所述中药组合物内包括中药原料药,所述中药原料药由以下重量份的中药材组成:生黄芪10~120份,白术10~60份,枸杞10~60份,杜仲10~60份,蝉蜕5~30份,青风藤10~60份,鬼箭羽10~75份,穿山龙10~75份,败酱草10~60份,金樱子10~75份,车前子10~30份,五味子10~75份,土鳖虫10~30份,当归10~60份。
优选地,所述中药原料药由以下重量份的中药材组成:生黄芪20-30份、白术10-15份、枸杞15-25份、杜仲15-20份、蝉蜕5-10份、青风藤30-40份、鬼箭羽15-20份、穿山龙15-20份、败酱草20-30份、金樱子30-40份、车前子10-15份、五味子15-20份、土鳖虫20-25份、当归10-30份。
优选地,所述中药原料药由以下重量份的中药材组成:生黄芪30份,白术15份,枸杞15份,杜仲15份,蝉蜕10份,青风藤30份,鬼箭羽20份,穿山龙20份,败酱草30份,金樱子30份,车前子15份,五味子20份,土鳖虫20份,当归10份。
优选地,所述中药原料药由以下重量份的中药材组成:生黄芪20份,白术10份,枸杞15份,杜仲15份,蝉蜕5份,青风藤30份,鬼箭羽15份,穿山龙15份,败酱草20份,金樱子30份,车前子10份,五味子15份,土鳖虫20份,当归10份。
黄芪:为豆科植物蒙古黄芪或膜夹黄芪的干燥根,味甘、性微温;归脾、肺经;为补气要药,临床应用时习惯分为生用、蜜炙、麸皮拌炒3种,其药效各有不同,生黄芪具有益气固表、托疮生肌、利水消肿等功效。主治内伤劳倦、脾虚泄泻、脱肛、气虚血脱、崩带、自汗、盗汗、血痹、浮肿、痈疽不溃或溃之不敛及一切气衰血虚之症。
白术:为菊科植物白术的干燥根茎,味苦、甘,性温;归肝、肾经;具有健脾益气,燥湿利水的功效;主治脾虚食少、消化不良、泄泻、水肿、自汗、胎动不安等症。
枸杞:为茄科植物宁夏枸杞的干燥成熟果实,枸杞味甘,性平;归肝、肾经;具有滋肾、润肺、补肝、明目等功效;主治肝肾阴亏、腰膝酸软、头晕目眩、目昏多泪、虚劳咳嗽、消渴、遗精等症。
杜仲:为杜仲科植物杜仲的干燥树皮,味甘,性微辛、温;归肝、肾经;具有补肝肾、强筋骨、安胎等功效;主治腰脊酸疼、足膝痿弱、小便余沥、阴下湿痒、胎漏欲堕等症。
蝉蜕:为蝉科昆虫黑蚱的若虫羽化时脱落的皮壳,味甘,性咸、寒;归肺、肝经;具有散风除热、利咽透疹、退翳明目、解痉的功效;主治风热感冒、咽痛、音哑、麻疹不透、风疹瘙痒、目赤翳障、惊风抽搐、破伤风等症。
青风藤:为防己科植物青藤和毛青藤的干燥藤茎,味苦、性平;归肝、脾经;具有祛风湿、通经络的功效;主治风湿痹痛、关节肿胀、麻痹瘙痒等症。
鬼箭羽:为卫矛科植物卫矛的具翅状物的枝条或翅状附属物,味苦,性寒,归肝经;具有破血通经、解毒消肿、杀虫的功效;主治癥瘕结块、心腹疼痛、闭经痛经、崩中漏下、产后瘀滞腹痛、恶露不下、疝气、历节痹痛、疮肿、跌打伤痛、虫积腹痛、烫火伤、毒蛇咬伤等症。
穿山龙:为薯蓣科植物穿龙薯蓣的干燥根茎,味苦、性平;归肝和肺经;具有祛风除湿、活血通络、止咳的功效;主治风湿痹痛、肢体麻木、胸痹心痛、慢性气管炎、跌打损伤、痈肿等症。
败酱草:为败酱科植物白花败酱的干燥全草。味辛、苦,性凉;归肝、胃、大肠经;具有清热解毒,消痈排脓,活血行瘀的功效,主治肠痈、肺痈及疮痈肿毒,实热瘀滞所致的胸腹疼痛,产后瘀滞腹痛等症。
金樱子:为蔷薇科植物金樱子的干燥成熟果实,味酸、甘、涩,性平;归肾、膀胱、大肠经;具有固精缩尿、固崩止带、涩肠止泻的功效;主治遗精滑精、遗尿尿频、崩漏带下、久泻久痢等症。
车前子:为车前科植物车前或平车前的干燥成熟种子,味甘,性寒;归肝、肾、肺、小肠经;具有清热利尿通淋、渗湿止泻、明目、祛痰的功效;主治热淋涩痛、水肿胀满、暑湿泄泻、目赤肿痛、痰热咳嗽等症。
五味子:为木兰科植物五味子的干燥成熟果实,味酸、甘,性温;归肺、心、肾经;具有收敛固涩、益气生津、补肾宁心的功效;主治久嗽虚喘、梦遗滑精、遗尿尿频、久泻不止、自汗盗汗、津伤口渴、内热消渴、心悸失眠等症。
土鳖虫:为鳖蠊科昆虫地鳖或冀地鳖的雌虫干燥体,味咸,性寒;归肝经;具有活血通络、化瘀行滞的功效;主治跌打损伤、筋伤骨折、血瘀经闭、产后瘀阻腹痛、瘾瘕痞块。
当归:为伞形科植物当归的干燥根,味甘、辛,性温;归肝、心、脾经;具有补血活血、调经止痛、润肠通便的功效;主治血虚萎黄、眩晕心悸、月经不调、经闭痛经、虚寒腹痛、风湿痹痛、跌扑损伤、痈疽疮疡、肠燥便秘等症。
本发明所提供的治疗膜性肾病的中药组合物中所含的各中药材可通过市售购买获取得到。
优选地,所述中药组合物还包括药学上可接受的辅料。
所述辅料可以包括但不限于溶剂、增溶剂、助溶剂、着色剂、崩解剂、填充剂、润滑剂、润湿剂、稳定剂、矫味剂、防腐剂、助悬剂、包衣材料、抗黏合剂、整合剂、增塑剂等。
具体地,所述辅料包括但不限于:蔗糖、淀粉、硬脂酸镁、甘露醇、山梨醇、山梨酸或钾盐、焦亚硫酸钠、亚硫酸氢钠、硫代硫酸钠、盐酸半胱氨酸、巯基乙酸、蛋氨酸、维生素A、维生素C、维生素E、维生素D、氮酮、EDTA二钠、EDTA钙钠,一价碱金属的碳酸盐、醋酸盐、磷酸盐或其水溶液、盐酸、醋酸、硫酸、磷酸、氨基酸、氯化钠、氯化钾、乳酸钠、木糖醇、麦芽糖、葡萄糖、果糖、右旋糖苷、甘氨酸、乳糖、甘露糖醇、纤维素及其衍生物、藻酸盐、明胶、聚乙烯吡咯烷酮、甘油、丙二醇、乙醇、吐温60~80、司盘~80、蜂蜡、羊毛脂、液体石蜡、十六醇、没食子酸酯类、三乙醇胺、碱性氨基酸、尿素、尿囊素、碳酸钙、碳酸氢钙、表面活性剂、聚乙二醇、环糊精、β~环糊精、磷脂类材料、高岭土、滑石粉、硬脂酸钙等。
取按上述重量份的中药材配制本发明所述的中药原料药,按药剂学常规方法,加入常规辅料,制备成各种临床可接受的给药剂型,这些给药剂型包括但不限于:片剂、胶囊剂、口服液、口含剂、颗粒剂、冲剂、丸剂、滴剂、散剂、膏剂、丹剂、混悬剂、粉剂、溶液剂、注射剂、栓剂、软膏剂、硬膏剂、霜剂、喷雾剂、贴剂,其中片剂可以为普通片剂、糖衣片剂、薄膜片剂,胶囊剂可以是硬胶囊剂或者软胶囊剂。
所述中药组合物的给药剂型优选胃肠道给药制剂,所述胃肠道给药制剂包括但不限于片剂、丸剂、散剂、胶囊剂、颗粒剂、冲剂、口服液、滴丸或者膏剂。
为了实现第二个目的,本发明所采取的技术方案是:
所述中药原料药的制备包括以下步骤:将各所述中药材混合均匀后碎成粉末,将所得粉末混合均匀制得;
或者所述中药原料药的制备主要包括以下步骤:将各所述中药材均匀混合,用溶剂提取混合均匀的中药材,制得中药提取液;将所制得的中药提取液进行浓缩,制得所述中药原料药。
或者所述中药原料药的制备主要包括以下步骤:将各所述中药材分别用溶剂提取制得中药提取液后,将所制得的中药提取液均匀混合;将混合均匀的中药提取液进行浓缩,制得所述中药原料药。
在本发明中,所述中药材经提取工艺得到的可直接用于制备制剂的任何形式的产物,例如是提取液、稠膏、固体物,固体物可以是固体颗粒或者是固体粉末,以上统称为中药原料药。
所述中药原料药可按照如下步骤制得:取各中药材混合均匀后粉碎制得中药材粉碎物,向中药材粉碎物中加入水,水的加入量是中药材总重量5~20倍,使用乙醇、水或乙醇水溶液煎煮或回流提取1~5次,每次0.5~5小时,合并提取液,过滤,滤液减压浓缩至相对密度为1.1~1.5(25℃)的稠膏,干燥,即得本发明所述的中药原料药。
其中,优选地,上述步骤中水的加入量为中药材总重量5~15倍;更优选地,水的加入量为中药材总重量8~12倍;
优选地,上述步骤中煎煮或者回流提取的次数为2~3次,煎煮或者回流提取时间为0.5~3小时,更优选地,煎煮或者回流提取时间为1~3小时;
优选地,上述步骤所制得的稠膏浓缩液的相对密度为1.2~1.4(25℃)。
所述中药原料药还可按照如下步骤制得:取各中药材混合均匀,粉碎得粉碎物,向粉碎物中加入水,水的加入量是中药材总重量的5~20倍,在80~100℃条件下煎煮或者回流提取0.5~5小时得提取液;将提取液过滤,滤液减压浓缩,干燥,即得本发明所述的中药原料药。
优选地,上述步骤中水的加入量是中药材总重量的5~15倍;更优选地,水的加入量是中药材总重量的8~12倍。
优选地,上述步骤中煎煮或者回流提取的次数为2~3次,煎煮或者回流提取时间优选0.5~3小时,更优选1~3小时。
所述中药原料药还可按照如下步骤制得:取各中药材混合均匀、粉碎制得中药粉碎物,向制得的中药粉碎物中加入水,水的加入量是中药材总量5~20倍,在80~100℃左右煎煮或者回流提取0.5~5小时;过滤,滤液减压浓缩成膏状;用2~5倍量50~90%的乙醇回流提取2~3次,将乙醇提取液于70~90℃去除乙醇,真空干燥,即得本发明所述的中药原料药。
优选地,上述步骤中水的加入量是中药材总重量的5~15倍;更优选地,水的加入量是中药材总重量的8~12倍;
优选地,上述步骤中煎煮或者回流提取的次数为2~3次,煎煮或者回流提取时间为0.5~3小时,更优选地,煎煮或回流提取的时间为1~3小时。
所述中药原料药还可按照如下步骤制得:将各所述中药材混合均匀,粉碎得粉碎物,向粉碎物中加入水,水的加入量是中药材总重量的5~20倍,在80~100℃左右煎煮提取0.5~5小时;水煎液浓缩至相对密度为1.1~1.5(25℃),加95%乙醇至乙醇浓度达到70%,放置过夜,过滤,浓缩滤液,干燥,即得本发明所述的中药原料药。
优选地,上述步骤中水的加入量是中药材总重量的5~15倍;更优选地,水的加入量为中药材总重量的8~12倍。
优选地,上述步骤中提取的次数为2~3次,提取时间为0.5~3小时,更优选地,提取时间为1~3小时。
优选地,上述步骤中制得的水煎浓缩液的相对密度为1.2~1.4(25℃)。
为实现的第三个目的,本发明所采取的技术方案是:
本发明第一目的所提供的任何一种所述中药组合物,在制备治疗和/或预防膜性肾病药物中的应用。
本发明具有如下优点:
膜性肾病多属中医学水肿、尿浊等范畴。根据本发明的发明人临床观察,膜性肾病患者多出现泡沫尿、浮肿、乏力纳呆、腰膝酸软等症,结合文献分析属脾肾亏虚、风湿扰络证。本发明所提供的中药组合物功效为健脾益肾、祛风除湿通络,针对膜性肾病核心病机脾肾亏虚、风湿扰络而设,可改善水肿、乏力等症状,降低尿蛋白,保护肾功能。且毒副作用不明显,安全性高。本发明所提供的中药组合物中生黄芪、白术健脾益气,枸杞、杜仲补肾填精,金樱子、五味子补肾固精,合以健脾益肾;蝉蜕、青风藤、穿山龙祛风胜湿通络,鬼箭羽、土鳖虫、当归活血化瘀通络,败酱草、车前子清热利湿解毒。诸药合用共奏健脾益肾、祛风除湿通络之功。
通过中药组合物对大鼠肾脏损伤的影响实验表明,相较模型组大鼠,各治疗组大鼠精神状态、活动反应、进食量、尿量、体重、毛色、水肿等一般情况均有所好转,各治疗组的24h-UTP及血清C5B-9均较模型组明显减少;各治疗组较模型组血清白蛋白水平有不同程度升高。
治疗膜性肾病的中药组合物对cBSA大鼠肾脏组织病理学的改变有明显的改善:
免疫荧光结果表明:各治疗组大鼠肾小球IgG、补体C3荧光沿肾小球毛细血管袢少量、颗粒样沉积,强度约为(+)-(+++),免疫荧光强度均较模型组明显减轻,但程度不一;
光镜结果表明:各治疗组大鼠肾小球肾小球体积增大不明显,毛细血管基底膜增厚不显著,少量“钉突”形成,病理改变均较模型组明显减轻,但程度不一;
电镜结果表明:各治疗组大鼠肾小球毛细血管基底膜增厚不明显,上皮细胞下可见少量电子致密物,足突部分融合,病理改变均较模型组明显减轻,但程度不一;
免疫组化结果表明,各治疗组的desmin蛋白的阳性染色面积明显少于模型组。
治疗膜性肾病的中药组合物可通过调控膜性肾病大鼠肾组织足细胞相关蛋白及自噬和凋亡相关蛋白的表达,从而减轻足细胞损伤:
治疗膜性肾病的中药组合物对cBSA大鼠肾小球足细胞相关蛋白表达水平的影响:Western Blot结果显示,与模型组相比,各治疗组大鼠肾组织Nephrin、synaptopodin、Podocin水平均显著升高;CD2AP水平出现不同程度升高。
治疗膜性肾病的中药组合物对cBSA大鼠肾小球足细胞相关蛋白mRNA表达水平的影响:PCR结果显示,与模型组相比,各治疗组可上调Nephrin、synaptopodin、CD2AP、Podocin的mRNA表达,下调desmin的mRNA表达。
治疗膜性肾病的中药组合物对cBSA大鼠肾小球足细胞自噬及凋亡相关蛋白的影响:Western Blot结果显示,与模型组相比,各治疗组大鼠肾组织Beclin1,Bcl2,LC3蛋白水平出现不同程度升高;P62、Caspase-3、Bax蛋白水平出现不同程度下降。
治疗膜性肾病的中药组合物对cBSA大鼠肾小球足细胞自噬及凋亡相关蛋白mRNA表达水平的影响:PCR结果显示,与模型组相比,各治疗组大鼠肾组织Beclin1、Bcl2、LC3mRNA含量出现不同程度升高;Caspase-3、Bax mRNA含量出现不同程度下降。
临床试验表明:本发明所提供的中药组合物可较快改善患者症状、减轻蛋白尿,疗效稳定且安全性较高。
现代药理研究发现,黄芪多糖、黄芪甲苷及毛蕊异黄酮苷等是黄芪的有效成分,利尿消肿效果显著,且可减轻大量利尿引起的电解质紊乱。黄芪多糖可以促进免疫器官发育,提高机体的免疫功能,并且可通过调控肾间质中相关蛋白的表达,抑制肾间质纤维化。
白术内酯Ⅲ是白术的主要活性成分,具有较强的抗氧化作用,可显著降低肾衰大鼠的血清肌酐、血尿素氮和尿蛋白水平并减轻线粒体损伤,增加抗氧化酶的活性,从而降低ROS的产生。白术的另一种活性成分白术内酯Ⅰ可通过靶向成纤维细胞-肌成纤维细胞分化以及上皮-间充质转化来抑制UUO大鼠肾脏纤维化发展。其抗纤维化作用与抑制由JAK2/STAT3,PI3K/Akt,p38/MAPK和Wnt/β-catenin等信号通路组成的增殖级联反应活性有关,进而减少间质和小管中的细胞过度增殖。
枸杞富含多糖、黄酮及多种微量元素,具有较强的抗氧化活性及免疫调节功能。研究发现枸杞提取物可显著降低链脲佐菌素(STZ)诱导的糖尿病肾病大鼠的血清肌酐、血清尿素氮、血清白蛋白和TGF-β1水平。并且可减少肾组织中GSH、SOD、CAT等氧化应激产物和IL-6和IL-1β等炎症因子的水平,进而保护肾脏功能完整。枸杞多糖可通过抑制NF-κB和AngII的表达来降低MCP-1和ICAM-1的表达延缓糖尿病肾脏病变的出现和发展。
杜仲活性包括木脂素类、有机酸类、黄酮类、和多糖类等,具有降压、抗炎、肝肾保护和抗肿瘤等药理作用。研究发现,杜仲提取物对糖尿病肾病和高血压肾损伤等引发的肾脏纤维化具有一定治疗作用。作用机制可能与抑制细胞增殖分化、抗氧化及抗炎等相关。
蝉蜕又名蝉衣,研究表明,蝉蜕中可提取出乙酰多巴胺二聚体,从而能改善脂质代谢,减少蛋白尿。蝉蜕提取物能调整NO功能,抑制血小板聚集,具有抗凝作用,可改善多种肾脏病出现的高凝状态。
青风藤又名寻风藤,主要含有挥发油、生物碱类、甾醇类等活性成分,其中青藤碱为吗啡烷类生物碱,为青风藤中的主要活性化学成分。青藤碱通过改善抗氧化作用中断TGF-β/Smad和Wnt/β-catenin的促纤维化信号的传导,激活Nrf2信号通路,调控巨噬细胞M1/M2极化,抑制IkBα磷酸化和NF-kB核易位,有效减低TGF-β诱导的肾小管上皮细胞纤维化模型中促纤维化蛋白表达,并能减弱UUO大鼠的肾脏纤维化。
鬼箭羽主要含有黄酮类、甾体类、生物碱类、挥发油类等活性成分,具有降糖、抑菌、抗炎、抗氧化等作用。研究表明鬼箭羽可通过调节血脂、血糖,改善机体免疫功能,减少炎性因子释放,抑制变态反应,减少氧化应激等作用进而减少免疫复合物沉积,保护肾小管上皮细胞,防治肾小球硬化。可下调TGF-β1进而降低DN大鼠HbA1c,降低血脂,减少24小时尿蛋白并减轻细胞外基质扩张和肾小球硬化。
穿山龙的有效成分包括薯蓣皂苷元、脱氧替告皂甙元、紫杉醇、薯蓣皂苷等,具有免疫调节作用,对多种自身免疫性疾病起到一定的治疗效果。薯蓣皂苷元与甾体激素类药物结构相近,是合成甾体激素的主要原料之一。薯蓣皂苷是其主要有效成分及活性成分,可通过抑制Wnt信号通路,下调TGF-β1表达进而保护系膜细胞。薯蓣皂苷在肾缺血再灌注损伤中能显著降低血清尿素氮和肌酐水平,减轻肾脏细胞损伤。
败酱草的主要成分有槲皮素、木樨草素、山柰酚、华防己碱等。槲皮素在多个细胞模型中具有抗炎作用,在大鼠乳鼠心脏成纤维细胞炎症分泌模型中,槲皮素能抑制NF-κB上游信号蛋白Akt的磷酸化,进而抑制转录因子NF-κB激活,减少其诱导的TNF-α、IL-1β等炎症因子的分泌。华防己碱又称青风藤碱,是一种单体生物碱,具有抗炎作用。木樨草素、山柰酚可抑制Iκβ和p65的磷酸化进而阻断NF-κB信号通路介导的炎症反应。
金樱子主要含有酚酸类、甾体类、维生素、三萜类、苯丙素等化学成分,具有抗氧化、抗炎、改善肾功能、提高机体免疫力等作用。金樱子提取物可抑制Sirt1/Nrf2/NF-κB信号通路减轻缺血再灌注大鼠模型的细胞损伤,显著降低其血清肌酐和血尿素氮水平及丙二醛、超氧化物歧化酶和谷胱甘肽过氧化物酶(GSH-Px)、ROS及促炎因子的的水平,具有明显的肾脏保护作用。
车前子主要含有苯乙醇苷类、环烯醚萜类、黄酮类、生物碱、萜类、多糖等成分,具有利尿、降血脂、抗炎、调节免疫、抗氧化、肾保护等药理作用。车前子水提取物可显著降低TNF-α及NO含量,同时抑制NF-κB向细胞核的转移,显示出良好的抗炎作用。车前子多糖可下调膜性肾病大鼠血清中BUN、SCr、TNF-α、IL-1β含量及蛋白尿水平,改善肾小球滤过功能。
五味子具有抗氧化、损伤修复、抗炎等多种药理活性。五味子提取物可显著降低链脲佐菌素诱导的DN小鼠模型尿白蛋白排泄率和尿白蛋白/肌酐比,减轻肾小球硬化,并通过抑制EMT防止足细胞丢失及裂孔膜损伤,保持足细胞完整性。
土鳖虫别称土元,具有溶解血栓、抗凝血、调节血脂等药理作用,可降低大鼠纤维蛋白原FIB含量、延长凝血酶原时间、降低血小板聚集率,起到抗凝血效果。同时可抑制细胞脂质过氧化反应,提高损伤血管内皮细胞分泌NO能力,表现出一定的血管内皮细胞保护作用。
当归的主要化学成分有挥发油、有机酸、多糖类、黄酮类等,具有抗炎、调节免疫、抗氧化等作用。研究表明当归可通过抑制肾小球毛细血管中的红细胞淤积和肾脏系膜细胞增生、减少肾小管损失,降低尿白蛋白含量,进而达到维护足细胞裂孔膜结构完整性、保护足细胞的作用。其抗炎作用机理主要涉及降低毛细血管通透性和抑制PGE2的合成或释放,对于慢性肾炎和轻微炎症的疗效较为明显。
附图说明
为了更清楚地说明本发明的实施方式或现有技术中的技术方案,下面将对实施方式或现有技术描述中所需要使用的附图作简单地介绍。显而易见地,下面描述中的附图仅仅是示例性的,对于本领域普通技术人员来讲,在不付出创造性劳动的前提下,还可以根据提供的附图引伸获得其它的实施附图。
本说明书所绘示的结构、比例、大小等,均仅用以配合说明书所揭示的内容,以供熟悉此技术的人士了解与阅读,并非用以限定本发明可实施的限定条件,故不具技术上的实质意义,任何结构的修饰、比例关系的改变或大小的调整,在不影响本发明所能产生的功效及所能达成的目的下,均应仍落在本发明所揭示的技术内容得能涵盖的范围内。
图1为本发明提供的中药组合物对cBSA大鼠尿蛋白及血清生化的影响:(A)中药组合物对cBSA大鼠24h尿蛋白定量的影响;(B)中药组合物对cBSA大鼠血清白蛋白的影响;(C)中药组合物对cBSA大鼠血清肌酐及尿素的影响;(D)中药组合物对cBSA大鼠血清甘油三酯及胆固醇的影响;(E)中药组合物对cBSA大鼠血清谷丙、谷草转氨酶的影响;(F)中药组合物对cBSA大鼠血清C5b-9的影响。
图2为本发明提供的中药组合物对大鼠肾组织影响的免疫荧光观察结果:A-G依次为空白组、模型组、中药组合物低剂量组、中药组合物中剂量组、中药组合物高剂量组、中药组合物高剂量+环孢素组和环孢素组大鼠肾脏IgG免疫荧光结果;H-N依次为空白组、模型组、中药组合物低剂量组、中药组合物中剂量组、中药组合物高剂量组、中药组合物高剂量+环孢素组和环孢素组大鼠肾脏C3免疫荧光结果;
图3为本发明提供的中药组合物对大鼠肾组织影响的光镜观察结果:A-G依次为空白组、模型组、中药组合物低剂量组、中药组合物中剂量组、中药组合物高剂量组、中药组合物高剂量+环孢素组和环孢素组大鼠肾脏Masson染色结果;H-N依次为空白组、模型组、中药组合物低剂量组、中药组合物中剂量组、中药组合物高剂量组、中药组合物高剂量+环孢素组和环孢素组大鼠肾脏PAS染色结果;O-U依次为空白组、模型组、中药组合物低剂量组、中药组合物中剂量组、中药组合物高剂量组、中药组合物高剂量+环孢素组和环孢素组大鼠肾脏PASM染色结果。
图4为本发明提供的中药组合物对大鼠肾组织影响的电镜观察结果:A-G依次为空白组、模型组、中药组合物低剂量组、中药组合物中剂量组、中药组合物高剂量组、中药组合物高剂量+环孢素组和环孢素组大鼠肾脏电镜观察结果。
图5为本发明提供的中药组合物对大鼠肾组织影响的desmin免疫组化观察结果,A-G依次为空白组、模型组、中药组合物低剂量组、中药组合物中剂量组、中药组合物高剂量组、中药组合物高剂量+环孢素组和环孢素组大鼠desmin免疫组化观察结果;H为desmin免疫组化统计结果。
图6本发明提供的中药组合物对cBSA大鼠肾小球足细胞相关蛋白及mRNA的影响,(A)大鼠肾组织足细胞相关蛋白表达;(B)大鼠肾组织自噬及凋亡相关蛋白表达;(C)大鼠肾组织足细胞相关蛋白表达量的统计结果;(D)大鼠肾组织足细胞相关mRNA表达量的统计结果;(E)大鼠肾组织自噬及凋亡相关蛋白表达量的统计结果;(F)大鼠肾组织自噬及凋亡相关mRNA表达量的统计结果。
具体实施方式
以下由特定的具体实施例说明本发明的实施方式,熟悉此技术的人士可由本说明书所揭露的内容轻易地了解本发明的其他优点及功效,显然,所描述的实施例是本发明一部分实施例,而不是全部的实施例。基于本发明中的实施例,本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例,都属于本发明保护的范围。
下面结合具体实施例对本发明作更进一步的说明,以便本领域的技术人员更了解本发明,但并不因此限制本发明。
本发明以下实施例中未注明具体条件的实验方法,均为在按照常规条件下进行。
本发明以下实施例中所用的原料或试剂除特别说明外,均市售可得。
一、中药组合物的制备:
实施例1
中药原料药的组成:生黄芪120g、白术50g、枸杞20g、杜仲30g、蝉蜕20g、青风藤10g、鬼箭羽10g、穿山龙10g、败酱草10g、金樱子20g、车前子50g、五味子50g、土鳖虫10g、当归10g。
中药组合物的制备:取上述组方中的中药材混合均匀,粉碎成粉末装入胶囊,每粒重0.3g,即得。
实施例2
中药原料药的组成:生黄芪80g、白术10g、枸杞10g、杜仲12g、蝉蜕10g、青风藤60g、鬼箭羽10g、穿山龙30g、败酱草30g、金樱子20g、车前子10g、五味子12g、土鳖虫30g、当归10g。
中药组合物的制备:取上述组方中的中药材混合均匀后粉碎,粉碎成过80目筛的粉末,加入蜂蜜,蜂蜜的加入量为中药材总重量的1/5,制成小丸,每丸约0.1g,即得。
实施例3:
中药原料药的组成:生黄芪10g、白术60g、枸杞60g、杜仲30g、蝉蜕20g、青风藤10g、鬼箭羽8g、穿山龙12g、败酱草15g、金樱子20g、车前子20g、五味子20g、土鳖虫1g、当归20g。
中药组合物的制备:将上述各中药材混合均匀后粉碎,粉碎成粉末装入胶囊,每粒重0.3g,即得。
实施例4:
中药原料药的组成:生黄芪15g、白术10g、枸杞10g、杜仲20g、蝉蜕5g、青风藤50g、鬼箭羽20g、穿山龙20g、败酱草12g、金樱子20g、车前子20g、五味子20g、土鳖虫10g、当归60g。
中药组合物的制备:取上述组方中的中药材混合均匀,加入水煎煮,水加入的量为中药材总重量的8倍,水煎1小时,过滤;滤渣再加入水煎煮,水的加入量为中药材总重量的5倍,煎煮1小时,过滤;合并煎液,浓缩至相对密度为1.15~1.25(25℃),加入糖精钠0.1%,灌装至玻璃瓶中,即得。
实施例5:
中药原料药的组成:生黄芪30g、白术30g、枸杞30g、杜仲30g、蝉蜕10g、青风藤20g、鬼箭羽10g、穿山龙10g、败酱草30g、金樱子20g、车前子10g、五味子10g、土鳖虫30g、当归30g。
中药组合物的制备:取上述组方中的中药材混合均匀,加入水煎煮1小时,水加入的量为中药材总重量的8倍;过滤,滤渣再加入水煎煮1小时,水加入的量为中药材总重量的5倍;过滤,合并煎液,浓缩至相对密度为1.15~1.25(25℃),喷雾干燥,得浸膏粉,加入与该浸膏粉等重量的淀粉,混合均匀,装胶囊,即得。
实施例6:
中药原料药的组成:生黄芪20g、白术12g、枸杞60g、杜仲30g、蝉蜕30g、青风藤60g、鬼箭羽75g、穿山龙75g、败酱草10g、金樱子75g、车前子30g、五味子10g、土鳖虫10g、当归60g。
中药组合物的制备:取上述组方中的中药材混合均匀,加入水煎煮1小时,水加入的量为中药材总重量的8倍;过滤,滤渣再加入水煎煮1小时,水加入的量为中药材总重量的5倍;过滤,合并煎液,浓缩至相对密度为1.15~1.25(25℃),加95%乙醇至醇浓度达70%,静置过夜,过滤,滤液喷雾干燥,得浸膏粉,加入该浸膏粉2倍重量的蔗糖,混合均匀,制粒,得到颗粒剂,即得。
实施例7:
中药原料药的组成:生黄芪60g、白术10g、枸杞10g、杜仲60g、蝉蜕30g、青风藤20g、鬼箭羽60g、穿山龙10g、败酱草30g、金樱子20g、车前子20g、五味子20g、土鳖虫10g、当归60g。
中药组合物的制备:将上述组方中的中药材混合均匀,加入水煎煮1小时,水加入的量为中药材总重量的6倍;过滤,滤渣再加入水煎煮1小时,水加入的量为中药材总重量的6倍;过滤,合并煎液,浓缩至相对密度为1.15~1.25(25℃),喷雾干燥,得浸膏粉;取以上浸膏粉1份,加2份淀粉、2份微晶纤维素,混合均匀,装胶囊,即得。
实施例8:
中药原料药的组成:生黄芪200g、炒白术100g、枸杞200g、杜仲200g、蝉蜕100g、青风藤400g、鬼箭羽200g、穿山龙155g、败酱草300g、金樱子400g、车前子150g、五味子200g、土鳖虫300g、当归150g。
中药组合物的制备:将上述组方中的中药材混合均匀,第一次加10倍量水煎煮1小时,第二次8倍量水煎煮1小时,煎液滤过,滤液合并,浓缩至相对密度为1.3(50℃-60℃),带式干燥,得中药组合物提取物,提取物中加入适量预胶化淀粉混合均匀,30%乙醇加入适量聚维酮K30作为粘合剂,流化床制成颗粒,干燥,即得。
实施例9:
中药原料药的组成:生黄芪20g、白术10g、枸杞15g、杜仲15g、蝉蜕5g、青风藤30g、鬼箭羽15g、穿山龙15g、败酱草20g、金樱子30g、车前子10g、五味子15g、土鳖虫20g、当归10g。
中药组合物的制备:按照实施例8的制备方法制备得到颗粒剂,装袋密封,每袋含中药组合物20.5g,即得。
以下结合具体的临床试验及动物药效学实验对本发明所提供的的药物组合物的有益效果作进一步的说明。
二、中药组合物对大鼠肾脏损伤的影响
1材料与方法
1.1材料
1.1.1实验药品
试药:按照实施例9的配方组成和制备方法制得的中药组合物,临用时用水溶解/混悬后供实验使用。
环孢素A,杭州中美华东制药有限公司,国药准字H10960123。
1.1.2实验动物
90只6周龄的健康雄性清洁级(specific path free,SPF)SD大鼠体重180±20g,购自北京维通利华实验动物技术有限公司(许可证号SCXK京2012-0001),置于洁净动物房,室内维持持续12h的光照,持续12h的避光循环处理,环境参数为22℃、湿度40%。为其提供相应的水与普通饲料(购自北京维通利华实验动物技术有限公司)。进行1周常规适应性喂养。整个实验过程符合天津中医药大学实验动物保护条例。
1.1.3实验试剂来源
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1.1.4实验仪器
名称 | 厂家 | 型号 |
低温高速离心机 | 赛默飞世尔科技(中国)有限公司 | Micro17 |
精密电子天平 | 梅特勒托利多仪器(上海)有限公司 | PL-203 |
自动脱水机 | 武汉俊杰电子有限公司 | JJ-12J |
纯水仪 | 青岛富勒姆科技有限公司 | FBZ2001-UP-P |
透析袋 | 北京索莱宝科技有限公司 | MD55-14-5-5 |
冷冻干燥机 | 东京理化器械株式会社 | FDU-1200 |
恒温水浴锅 | 常州亿通分析仪器制造有限公司 | HH-W420 |
恒温箱 | 天津市莱玻瑞仪器设备有限公司 | GFL-230 |
超低温冰箱 | 海尔集团 | DW-86L626 |
多功能数显PH计 | 上海雷磁 | PHSJ-4F |
石蜡包埋机 | 上海徕卡仪器有限公司 | SK10310 |
冰冻切片机 | 上海徕卡仪器有限公司 | CM1950 |
石蜡切片机 | 上海徕卡仪器有限公司 | RM2016 |
正置光学显微镜 | 尼康仪器(上海)有限公司 | Nikon Eclipse E100 |
透射电子显微镜 | 捷欧路(北京)科贸有限公司 | JEM-1400 |
分光光度计 | Therno scientific | NANODROP2000 |
Western Blot | 美国Bio-Rad公司 | |
全波长酶标分析仪 | 赛默飞世尔科技(中国)有限公司 | THM51119300 |
多功能成像仪 | 德国耶拿分析仪器股份公司 | UVP Chemstudio touch |
Epgiadients PCR仪 | ||
实时荧光定量PCR仪 | 罗氏 | LightCycler96 |
1.1.5实验器械
血管钳、中弯钳、中直钳、组织剪、小剪、眼科镊、刀柄、刀片、持针器、1mL注射器、5mL注射器、无菌手套、纱布、棉签、EP管、大鼠固定器、冻存管、液氮罐等。
1.2实验方法
1.2.1透析袋的预处理
根据需要,将透析袋裁剪为适当长度(30-40cm),随后使用50%乙醇煮沸1小时以除去具有紫外吸收的杂质;在2%碳酸氢钠和1mmol/L EDTA(pH 8.0)中煮沸10分钟,以除去极微量的硫化物和重金属,使用蒸馏水彻底清洗透析袋,再次将其放入煮沸的1mmol/LEDTA(pH 8.0)中10分钟,室温冷却后,把透析袋始终浸没在溶液内存放于4度,注意从此时起取用透析袋必须佩戴手套操作,使用前将透析管用蒸馏水彻底清洗干净后即可使用。
1.2.2实验药品配制
1.2.2.1醋酸盐缓冲液配置
取100mL由冰醋酸稀释的4mol/L醋酸溶液加入醋酸铵31g,充分搅拌溶解,调整PH值为4.75。
1.2.2.2阳离子化牛血清白蛋白(cBSA)制备
取67mL无水乙二胺(EDA),加入500mL双蒸水充分混匀,然后再加入6mol/L盐酸350mL,调整混合溶液PH值到4.75,冷却并保持溶液温度为25℃。取5g牛血清白蛋白(BSA)溶于25mL蒸馏水后,边搅拌边将之加入前EDA溶液中,搅拌完全直至BSA完全溶解后再加1.8g碳二亚胺盐酸盐(EDC),持续搅拌2h使之充分反应,保持PH值为4.75,最后加入4mol/L PH值为4.75的醋酸盐缓冲液30mL终止反应,即得到等电点提高的cBSA溶液。将cBSA溶液置于透析袋中于4℃的双蒸水中透析72h(2-3h换水一次),真空冷冻干燥后,即得cBSA冻干粉。用聚丙烯酰胺等测定其等电点大于8.6即可,-80℃保存备用。
1.2.3大鼠膜性肾病模型建立
1.2.3.1预免疫
大鼠适应性喂养1周后,收集24小时尿液测定24h尿蛋白定量(24h-UTP)均小于5mg,尿蛋白阴性。随后将大鼠随机分成空白组15只,造模组80只。造模组:由于弗氏完全佐剂是标准的诱生体液免疫和细胞免疫的佐剂,主要诱导Th1型细胞因子的产生,而弗氏不完全佐剂则只诱导Th2型细胞因子,诱导机体产生抗体,弗氏完全佐剂抗原的含量有助于改善和延长免疫反应,其免疫强度大于费氏不完全佐剂。因而于预免疫第1日,取制备好的cBSA冻干粉1mg溶于0.5mL PBS中,与等体积的弗氏完全佐剂混合,制成乳化液。于模型组大鼠腋窝、腹股沟及肚脐旁等区域内的6个不同部位进行皮下注射,每处0.05mL,每只注射总体积为0.3mL。第2日起,同样将1mg cBSA冻干粉溶于0.5mL PBS中,与等体积的弗氏不完全佐剂混合后,于造模组大鼠相同部位相同体积皮下注射,持续6日。空白组:每只取PBS 0.5mL与弗氏不完全佐剂0.5mL混合乳化后,将所配药物与造模组同法于空白组大鼠皮下注射,持续7日。
1.2.3.2正式免疫
1周后,取制备好的cBSA冻干粉1mg溶于PBS 0.5mL中,于造模组大鼠尾静脉注射,每次以cBSA质量计16mg/kg,隔日1次,在第3周开始将注射剂量逐渐增加至25mg/kg。空白组大鼠给予等体积的PBS尾静脉注射,隔日1次,连续4周。于第5周测定大鼠24h-UTP,并随机观察实验大鼠肾脏病理,若24h-UTP超过20mg和(或)肾脏病理结果符合膜性肾病诊断结果即为造模成功。
1.2.4实验分组及给药
将80只造模组大鼠随机分为模型组15只、治疗膜性肾病的中药组合物低剂量组15只、治疗膜性肾病的中药组合物中剂量组15只、治疗膜性肾病的中药组合物高剂量组15只、环孢素组15只和治疗膜性肾病的中药组合物高剂量+环孢素组15只。
预免疫结束后即开始灌胃,每日1次,连续4周:
治疗膜性肾病的中药组合物低剂量组:每次灌胃前测量体重,根据体重给予治疗膜性肾病的中药组合物1.85g/Kg灌胃;
治疗膜性肾病的中药组合物中剂量组:每次灌胃前测量体重,根据体重给予治疗膜性肾病的中药组合物3.70g/Kg灌胃;
治疗膜性肾病的中药组合物高剂量组:每次灌胃前测量体重,根据体重给予治疗膜性肾病的中药组合物7.40g/Kg灌胃;
环孢素组:每次灌胃前测量体重,根据体重给予环孢素9.0mg/Kg灌胃;
环孢素+治疗膜性肾病的中药组合物高剂量组:每次灌胃前测量体重,根据体重给予治疗膜性肾病的中药组合物7.40g/Kg和环孢素9.0mg/Kg灌胃;
空白组、模型组:根据体重给予等体积的生理盐水灌胃。
2观察内容
2.1大鼠一般状态
每日对全部大鼠的一般情况进行观察并记录,包括其精神状态、皮毛光泽、活动、饮食、体重等。
2.2样本留取及处理
24h尿样本留取:在造模前及正式免疫结束后分别于代谢笼中留取各组大鼠的24h尿液,尿液留取过程中禁食不禁水。24h后收集总尿液并记录尿量。
肾脏组织留取:造模结束,麻醉后处死大鼠,迅速剖取肾脏,剥离包膜及周围脂肪组织,将肾脏组织分为3份,分别置于生理盐水浸湿的纱布、4%多聚甲醛、电镜固定液及液氮中用于免疫荧光、光镜和免疫组化、透射电镜及qRT-PCR和Western Blot检测。
血清留取:用10%水合氯醛腹腔注射麻醉大鼠,腹主静脉采血5mL,静置0.5h后,3000转/分钟离心10min分离血清后,取上清液分别装于EP管中,-20℃冰箱保存。
2.3生化指标检测
采用南京建成生物有限公司试剂盒,分别按试剂盒方法检测各大鼠血清尿素氮(BUN)、血肌酐(Scr)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、白蛋白(ALB)、胆固醇(TC)、甘油三酯(TG)及尿液24h尿蛋白定量(24h-UTP)等生化指标检测。
2.4ELISA检测大鼠血清中C5b-9的含量
a.标准品的稀释:准备小试管6只,依次编好号码,先在各小试管中加入标准品稀释液100μL,然后取原浓度标准品100μL加入一只已编好号的试管中,充分混匀;再在该试管中取100μL加入第二支试管中,充分混匀;再在该试管中取100μL加入第三只试管中,充分混匀;再在该试管中取100μL加入第四只试管中,充分混匀;再在该试管中取100μL加入第五只试管中,充分混匀;然后在该试管中取100μL,弃掉。第六只试管作为0号标准品。稀释后各管浓度分别是:2400pg/ml,1200pg/ml,600pg/ml,300pg/ml,150pg/ml,0pg/ml。在酶标包被板上设标准品孔,依次加入不同浓度的标准品50μL;
b.加样:分别设空白孔、待测样品孔。在酶标包被板上待测样品孔中先加样品40μL,然后再加生物素标记的抗C5b-9抗体10μL。加样将样品加于酶标板孔底部,尽量不触及孔壁,轻轻晃动混匀;
c.加酶:每孔加入酶标试剂50μL,空白孔除外;
d.温育:用封板膜封板后置37℃温育30分钟;
e.配液:将30倍浓缩洗涤液用蒸馏水30倍稀释后备用;
f.洗涤:小心揭掉封板膜,弃去液体,甩干,每孔加满洗涤液,静置30秒后弃去,如此重复5次,拍干;
g.显色:每孔先加入显色剂A50μL,再加入显色剂B50μL,轻轻震荡混匀,37℃避光显色10分钟;
h.终止:每孔加终止液50μL,终止反应(此时蓝色立转黄色);
i.测定:以空白孔调零,450nm波长依序测量各孔的吸光度(OD值)。测定应在加终止液后15分钟以内进行;
j.以标准物的浓度为横坐标,OD值为纵坐标,在坐标纸上绘出标准曲线,根据样品的OD值由标准曲线查出相应的浓度;或用标准物的浓度与OD值计算出标准曲线的直线回归方程式,将样品的OD值代入方程式,计算出样品浓度,即为样品的实际浓度。
2.5免疫荧光观察
将肾组织从湿润的纱布上取出,OCT包埋,冰冻切片机-22℃速冻10min,切成4μm的薄片,冷丙酮固定5min,PBS浸洗3遍,滴加一抗(IgG 1:200,C3 1:200)20μL,置于湿盒内避光37℃孵育30min,PBS浸洗3次,每次5min;滴加二抗(CY3山羊抗小鼠1:100)20μL覆盖组织,再次置于湿盒内避光37℃孵育30min;PBS浸洗3次,每次5min;抗荧光淬灭封片剂封片;荧光显微镜下观察,拍照记录。根据显微镜下荧光强度观察肾脏组织标本的荧光强度,用(-)表示无荧光;(+)为极弱的可疑荧光;(++)为荧光较弱但清楚可见;(+++)为荧光明亮;(++++)为荧光闪亮。
2.6光镜观察
肾脏组织置于4%多聚甲醛固定24h-48h后,酒精梯度脱水,经透明、浸蜡、包埋、常规切片和脱蜡至水制成3μm的切片。并按照操作步骤分别行PAS、Masson和PASM染色,光学显微镜下观察肾小球变化。
2.7电镜观察
大小约米粒样的大鼠肾皮质经电镜固定液固定1h后,在4℃1%锇酸中固定2h PBS充分清洗,乙醇梯度及100%丙酮脱水,丙酮和树脂混合液中浸透后于树脂中再次浸透,室温环氧树脂包埋,超薄切片,醋酸铀、柠檬酸铅染色,透射电镜下观察肾脏组织形态改变情况、拍照记录。
2.8免疫组化法检测肾组织Desmin的表达水平
采用免疫组化两步法(PV二步法)检测肾组织Desmin的表达水平。每组于实验结束后取6只大鼠肾组织经体积分数10%中性甲醛固定,梯度乙醇脱水,二甲苯透明,石蜡包埋,切片,脱蜡水化,用PBS(PH 7.4)清洗3次,体积分数3%H2O2室温封闭10min,EDTA高压修复,滴加兔抗大鼠Desmin,湿盒内4℃孵育过夜,生物素化二抗孵育,DAB显色5-10min,蒸馏水冲洗后苏木精复染,二甲苯透明,中性树胶封固,光学显微镜观察。Desmin以肾实质细胞胞浆内棕色颗粒为阳性。每张切片随机选取5个400倍视野,显微镜图像分析处理系统计算肾小球及肾小管中的Desmin的平均积分吸光度。
2.9Western Blot实验步骤
2.9.1组织蛋白提取
a.取大鼠肾皮质组织称量后切成较小的组织块(0.1~1.0g),加入400μL RIPA裂解液和1mL蛋白酶抑制剂,放入组织匀浆器中至组织研磨完全;
b.超声处理后冰上孵育0.5小时;
c.室温10000g/min离心10min后取中层溶液即为所提取蛋白溶液。
3.9.2BCA浓度测定:
a.使用PBS将标准品储存液稀释至25~2000μg/ml后,将其按0,1,2,4,8,12,16,20μL分别加入96孔板中,加标准品稀释液补足到20μL;
b.将适量体积的待测样品分别加入96孔板中,加标准品稀释液补足到20μL;
c.各孔中分别加入200μL BCA工作液(试剂盒中的A液和B液按50:1比例配制),充分混匀后,37℃孵育30分钟。
d.酶标仪测定562nm的吸光值,绘制蛋白浓度标准曲线,计算各个样品蛋白的实际浓度。
2.9.3蛋白变性
根据蛋白定量结果,使用RIPA调整样品蛋白终浓度为4μg/μL。将相应体积的蛋白样品与5×蛋白质凝胶电泳上样缓冲液(SDS-PAGE loading buffer)混匀,95℃煮沸10分钟待用。
2.9.4电泳
将蛋白样品加入到SurePAGETM蛋白预制胶的凝胶孔中,电泳仪设置成稳压状态,接通电源,浓缩胶恒压为80V,分离胶恒压120V。电泳至溴酚蓝染料至分离胶适当位置即可终止电泳。
2.9.5转膜
剪一较凝胶略大的PVDF膜置于甲醇中浸泡10s,然后将其置于转膜液中以平衡离子浓度;将样品胶与膜除去胶与膜之间的气泡后装入标有正、负极的转膜夹板中,放入含有快速转膜缓冲液的转膜槽中;将转膜槽置于盛有冰水混含物中降温,连接电源,使用恒流400mA转膜30min。
转膜完成后取出PVDF膜置于快速封闭液中,室温封闭15min;用TBST漂洗1次。使用一抗稀释液将一抗稀释成适宜浓度;将封闭后的PVDF膜放入一抗中,4℃反应过夜;次日,用1×TBST洗膜三次,每次10分钟;使用二抗稀释液将HRP标记山羊抗兔抗体稀释到1:5000,室温孵育膜60min;再次用1×TBST洗膜三次,每次10分钟;将膜浸入ECL发光液中,反应1min;根据不同的发光强度调整曝光;最后用image J软件分析蛋白条带灰度值。
2.10PCR检测步骤
2.10.1提取样本总RNA
a.称取30mg大鼠肾脏组织样品,使用液氮研磨后,转移至1.5mL离心管中,加入1mLRNAReagent(使用前每1mL RNA/>Reagent加入20μlβ-巯基乙醇),涡旋混匀,室温静置5min;
b.加入200μL氯仿,高速震荡20s,室温下静置2-3min;
c.在4℃下,12,000xg离心15min;
d.转移上清(约80%)至一新的离心管中,加入等体积的70%乙醇到上清液中,涡旋混匀;
e.将RNA结合柱套入收集管中,转移第4步得到的混合液(每次转移的混合液≤700μl),室温10000xg离心1min,弃滤液;
f.重复步骤e,直至所有混合液都结合到RNA结合柱上;
g.将RNA结合柱套入到2mL收集管中,加入500μl RNA Wash Buffer I至结合柱中,10000xg离心30s,弃滤液;
h.将RNA结合柱套回收集管中,加入500μL RNA Wash Buffer II(使用无水乙醇对RNA Wash Buffer II进行稀释,稀释后室温保存)至结合柱中,10000xg离心1min,弃滤液;
i.重复步骤h;
j.将RNA结合柱套回收集管中,10000xg离心空甩2min;
k.将RNA结合柱套入新的1.5mL离心管中,加入45-75μL DEPC Water至结合柱中,10000xg离心2min洗脱RNA,产物放置-80℃保存。
2.10.2RNA定量
使用Nanodrop 2000测量每组所提RNA核酸浓度,根据所读取到的RNA样品于260nm波长和280nm波长处的OD值,计算以A260/280比值。所提RNA A260/280比值在1.8-2.2之间,即证明RNA的纯度高,无污染,可用于后续实验。
2.10.3逆转录
用HiFiScript cDNA Synthesis Kit进行逆转录,实验操作按产品说明书进行,步骤如下:
a.将RNA模板、Primer Mix、dNTP Mix、DTT、RT Buffer、HiFiScript和RNase-FreeWater溶解并置于冰上备用。
b.根据以下配制反应体系,总体积为20μL。
试剂 | 20μL反应体系 | 终浓度 |
dNTP Mix,2.5mM Each | 4μL | 500μM Each |
Primer Mix | 2μL | |
RNA Template | XμL | |
5×RT Buffer | 4μL | 1× |
DTT,0.1M | 2μL | 10mM |
HiFiScript,200U/μL | 1μL | |
RNase-Free Water | Up to 20μL |
c.涡旋震荡混匀,短暂离心,使管壁上的溶液收集到管底。
d.42℃孵育15分钟,85℃孵育5分钟。反应结束后,短暂离心,置于冰上冷却。
e.逆转录产物可直接用于荧光定量PCR反应,或置于-20℃长期保存。
2.10.4RealTime PCR
用UltraSYBR Mixture(Low ROX)进行扩增,根据大鼠相关mRNA的全基因序列设计引物,并由生工生物工程(上海)股份有限公司进行引物合成。引物序列如下:
引物名称 | 引物序列(5'-3') | 片段长度(bp) |
R-GAPDH-S | CTGGAGAAACCTGCCAAGTATG | 138 |
R-GAPDH-A | GGTGGAAGAATGGGAGTTGCT | |
R-CD2AP-S | CCTACCTCACCTATGCCATCTCC | 221 |
R-CD2AP-A | GTTACCTCCACATTCTGGGTTCTA | |
R-synaptopodin-S | CCTAGTGGCATCAGCAGAACAA | 176 |
R-synaptopodin-A | TGGGACTTTGCTCTATCTGGCT | |
R-beclin1(1)-S | AGGAGTTGCCGTTGTACTGTTCT | 178 |
R-beclin1(1)-A | GTGTCTTCAATCTTGCCTTTCTCC | |
R-P62-S | TGTGGTGGGAACTCGCTATAAG | 176 |
R-P62-A | AGTGCCCATGTTTCAGCTTCC | |
R-LC3-S | TATCTGGGCATTTTGAAGACCTG | 171 |
R-LC3-A | GTCGGATGTCCAGAAGGTCAAT | |
R-itgB3(1)-S | TGTGCTAACACTAACCGACCAGG | 189 |
R-itgB3(1)-A | TGGGTCTTGGCATCAGTGGT |
PCR反应体系为:
试剂 | 50μL反应体系 | 终浓度 |
2×μLtraSYBR Mixture(Low ROX) | 25μL | 1× |
Forward Primer,10μM | 1μL | 0.2μM |
Reverse Primer,10μM | 1μL | 0.2μM |
Template DNA | 2μL | |
ddH2O | up to 50μL |
反应条件为:
步骤 | 温度 | 时间 |
预变性 | 95℃ | 10min |
变性 | 95℃ | 10s |
退火 | 56-64℃ | 30s |
延伸 | 72℃ | 32s |
融解曲线分析 | ||
95℃ | 15s | |
60℃ | 1min | |
95℃ | 15s | |
60℃ | 15s |
反应结束后,从仪器中拷贝出数据,采用2△△CT法进行数据的相对定量分析。
3统计分析
实验数据利用SPSS 26.0统计分析软件进行分析,计量资料以(均数±标准差)表示,各组数据比较前先进行正态性及方差齐性检验。对于符合正态分布的数据,用ANOVA进行多组间比较分析,若方差齐采用Tukey法,若方差不齐采用Dunnett's T3法。若数据为非正态分布,则改用非参数检验。以P<0.05为差异有统计学意义。
4结果
4.1大鼠一般状况
正常组大鼠精神状态良好,活动反应灵敏,饮食饮水较好,毛发有光泽。其他各造模组大鼠出现进食量减少,精神萎靡,活动减少,眯眼,体形消瘦,食少抱团,便搪,体毛欠光泽,耸毛,甚至出现毛发脱落,尿量增多,部分造模大鼠出现腹部胀大、四肢及阴囊不同程度水肿。期间,共有4只大鼠死亡,推测其死亡原因可能为预免疫期间因过敏而死亡。相较模型组大鼠,各治疗组大鼠精神状态、活动反应、进食量、尿量、体重、毛色、水肿等一般情况均有所好转。
4.2治疗膜性肾病的中药组合物对cBSA大鼠24h-UTP的影响
实验结束后,除空白组外,造模组大鼠与实验前比较均出现明显的蛋白尿,提示造模成功(P<0.01)。各治疗组较模型组24h-UTP均明显减少,差异显著(P<0.01);与治疗膜性肾病的中药组合物低剂量组相比,治疗膜性肾病的中药组合物高剂量+环孢素组减少最明显,差异有统计学意义(P<0.05);与环孢素组相比较,治疗膜性肾病的中药组合物各治疗组24h-UTP未见明显差异(P>0.05),实验结果见图1A和表1。
表1.24h尿蛋白定量及血清白蛋白的变化
注:与实验前对应组别相比:△P<0.01;与空白组相比:○P<0.01;与模型组相比:**P<0.01,*P<0.05;与治疗膜性肾病的中药组合物低剂量组相比:□P<0.01。
4.3治疗膜性肾病的中药组合物对cBSA大鼠ALB的影响
实验结束后,与空白组相比,模型组ALB显著下降,差异有统计学意义(P<0.05);与模型组相比,治疗膜性肾病的中药组合物低剂量组ALB虽有升高,但差异无统计学意义(P>0.05);治疗膜性肾病的中药组合物中、高剂量组,治疗膜性肾病的中药组合物高剂量+环孢素组及环孢素组较模型组ALB均不同程度升高,差异明显(P<0.05),以治疗膜性肾病的中药组合物高剂量+环孢素组最为显著;治疗膜性肾病的中药组合物中、高剂量组与环孢素组相比,差异不明显,无统计学意义(P>0.05),见图1B和表1。
4.4治疗膜性肾病的中药组合物对cBSA大鼠BUN、Scr的影响
实验结束后,与空白组相比,模型组及各治疗组大鼠BUN、Scr水平无明显差异(P>0.05);与模型组相比,各治疗组大鼠BUN、Scr水平亦无明显差异(P>0.05);各治疗组之间相比亦无明显差异(P>0.05),实验结果见图1C和表2。
4.5治疗膜性肾病的中药组合物对cBSA大鼠TC、TG的影响
实验结束后,与空白组相比,模型组TC、TG显著升高,差异有统计学意义(P<0.01);与模型组相比,治疗膜性肾病的中药组合物高剂量组、治疗膜性肾病的中药组合物高剂量+环孢素组与环孢素组TC明显下降,差异具有统计学意义(P<0.05),治疗膜性肾病的中药组合物各剂量组、治疗膜性肾病的中药组合物高剂量+环孢素组与环孢素组TG显著下降,差异具有统计学意义(P<0.01);与治疗膜性肾病的中药组合物低剂量组相比,中、高剂量组及治疗膜性肾病的中药组合物高剂量+环孢素组下降更明显,以治疗膜性肾病的中药组合物高剂量+环孢素组下降最明显,但无统计学意义(P>0.05);与环孢素组相比,治疗膜性肾病的中药组合物各剂量组的TC和TG水平均无明显差异(P>0.05),实验结果见图1D和表2。
4.6治疗膜性肾病的中药组合物对cBSA大鼠ALT、AST的影响
实验结束后,与空白组相比,模型组及各治疗组大鼠ALT、AST水平无明显差异(P>0.05);与模型组相比,各治疗组大鼠ALT、AST水平亦无明显差异(P>0.05);治疗膜性肾病的中药组合物高剂量+环孢素组和环孢素组个别大鼠ALT,以及环孢素组个别大鼠AST虽升高,但差异无统计学意义(P>0.05),其余各治疗组之间相比亦无明显差异(P>0.05),实验结果见图1E和表2。
表2.血清生化的比较
组别 | 数量 | BUN(mmol/L) | Scr(μmol/L) | TC(mmol/L) | TG(mmol/L) | ALT(U/L) | AST(U/L) |
a | 15 | 6.57±0.30 | 39.61±3.16 | 1.20±0.055 | 0.50±0.01 | 7.90±1.05 | 19.46±1.93 |
b | 13 | 6.57±0.39 | 42.09±2.42 | 2.02±0.11○ | 1.01±0.10○ | 7.21±0.49 | 19.56±1.28 |
c | 15 | 6.45±0.42 | 41.44±2.53 | 1.77±0.13 | 0.74±0.02** | 7.86±1.24 | 19.71±1.66 |
d | 15 | 6.32±0.41 | 40.24±3.87 | 1.67±0.04 | 0.72±0.03** | 7.71±1.03 | 18.77±1.66 |
e | 14 | 5.75±1.01 | 41.70±2.05 | 1.60±0.03* | 0.68±0.06** | 7.38±1.36 | 19.38±2.18 |
f | 14 | 6.28±0.41 | 41.70±3.17 | 1.52±0.08* | 0.67±0.05** | 18.41±19.68 | 18.95±1.96 |
g | 15 | 6.42±0.46 | 40.92±1.65 | 1.60±0.01* | 0.70±0.04** | 18.79±20.44 | 27.19±12.37 |
a,空白组;b,模型组;c,治疗膜性肾病的中药组合物低剂量组;d,治疗膜性肾病的中药组合物中剂量组;e,治疗膜性肾病的中药组合物高剂量组;f,治疗膜性肾病的中药组合物高剂量+环孢素组;g,环孢素组;与空白组相比:○P<0.01;与模型组相比:**P<0.01,*P<0.05。
4.7治疗膜性肾病的中药组合物对cBSA大鼠血清C5b-9的影响
实验结束后,与空白组相比,模型组大鼠C5b-9水平显著增加,差异有统计学意义(P<0.05);与模型组相比,各治疗组C5b-9水平均不同程度升高,差异显著(P<0.05);治疗膜性肾病的中药组合物各剂量组与环孢素组相比,差异不明显,无统计学意义(P>0.05);与其他治疗组相比,治疗膜性肾病的中药组合物高剂量+环孢素组升高最明显,差异具有统计学意义(P<0.05),实验结果见图1F和表3。
表3.血清C5b-9的比较
注:与Control组相比:○P<0.01;与MN组相比:**P<0.01,*P<0.05。
4.8治疗膜性肾病的中药组合物对cBSA大鼠肾脏组织病理学的改变影响
免疫荧光:空白组大鼠肾小球荧光强度(-);模型组大鼠肾小球免疫荧光可见IgG及补体C3荧光沿毛细血管袢弥漫性沉积,约为(+++)-(++++);各治疗组大鼠肾小球IgG、补体C3荧光沿肾小球毛细血管袢少量、颗粒样沉积,强度约为(+)-(+++),免疫荧光强度均较模型组明显减轻,但程度不一,实验结果见图2。
光镜:空白组大鼠肾小球形态未见明显改变;模型组大鼠肾小球体积增大,毛细血管基底膜弥漫性增厚,大量“钉突”形成;与模型组相比,各治疗组大鼠肾小球肾小球体积增大不明显,毛细血管基底膜增厚不显著,少量“钉突”形成,病理改变均较模型组明显减轻,以治疗膜性肾病的中药组合物高剂量+环孢素组最为显著,实验结果见图3。
电镜:空白组大鼠肾小球足细胞结构清晰,足突排列整齐,未见明显异常;模型组大鼠肾小球毛细血管基底膜明显增厚,上皮细胞下可见大量电子致密物沉积,足突广泛融合,钉突形成;与模型组相比,各治疗组大鼠肾小球毛细血管基底膜增厚不明显,上皮细胞下可见少量电子致密物,足突部分融合,病理改变均较模型组明显减轻以治疗膜性肾病的中药组合物高剂量+环孢素组最为显著,实验结果见图4。
免疫组化:正常情况下,Desmin蛋白在肾脏足细胞中仅微弱表达甚至不表达。与空白组相比,模型组大鼠肾小球内Desmin蛋白在毛细血管壁沿基底膜呈线性分布,出现了较强的阳性表达,Desmin蛋白表达显著增加,差异具有统计学差异(P<0.01);与模型组相比,各治疗组的阳性染色面积明显少于模型组(P<0.05),且以治疗膜性肾病的中药组合物高剂量+环孢素组效果最为明显;治疗膜性肾病的中药组合物各剂量组、环孢素组与治疗膜性肾病的中药组合物高剂量+环孢素组相比无明显差异(P>0.05),实验结果见图5。4.9治疗膜性肾病的中药组合物对cBSA大鼠肾小球足细胞相关蛋白表达水平的影响
WB检测大鼠肾小球足细胞相关蛋白表达水平的变化。结果显示,与空白组相比,模型组大鼠肾组织Nephrin水平显著降低(P<0.01)。与模型组相比,各治疗组大鼠肾组织Nephrin水平均显著升高(P<0.01),以治疗膜性肾病的中药组合物高剂量+环孢素组升高最为明显。治疗膜性肾病的中药组合物高剂量组与环孢素组相比无明显差异(P>0.05),实验结果见图6,表4。
与空白组相比,模型组大鼠肾组织synaptopodin水平显著降低(P<0.01)。与模型组相比,治疗膜性肾病的中药组合物中剂量组、治疗膜性肾病的中药组合物高剂量组、治疗膜性肾病的中药组合物高剂量+环孢素组及环孢素组大鼠肾组织synaptopodin水平显著升高(P<0.01)以治疗膜性肾病的中药组合物高剂量+环孢素组升高最为明显,治疗膜性肾病的中药组合物低剂量组synaptopodin水平虽有升高,但差异无统计学意义(P>0.05);治疗膜性肾病的中药组合物中、高剂量组与环孢素组相比无明显差异(P>0.05),实验结果见图6,表4。
与空白组相比,模型组大鼠肾组织CD2AP水平显著降低(P<0.01)。与模型组相比,治疗膜性肾病的中药组合物高剂量+环孢素组大鼠肾组织CD2AP水平显著升高(P<0.01),环孢素组明显升高(P<0.05);治疗膜性肾病的中药组合物各剂量组虽有升高,但差异无统计学意义(P>0.05);治疗膜性肾病的中药组合物各剂量组与环孢素组相比无明显差异(P>0.05),实验结果见图6,表4。
与空白组相比,模型组大鼠肾组织Podocin水平显著降低(P<0.01)。与模型组相比,与模型组相比,各治疗组大鼠肾组织Podocin水平均显著升高(P<0.01)以治疗膜性肾病的中药组合物高剂量+环孢素组升高最为明显;治疗膜性肾病的中药组合物高剂量组与环孢素组相比无明显差异(P>0.05),实验结果见图6,表4。
表4大鼠肾组织足细胞相关蛋白表达/>
与空白组相比:**P<0.01;与模型组相比:##P<0.01,#P<0.05;与环孢素组相比:●P>0.05。
PCR结果显示,与空白组相比,模型组Nephrin的mRNA表达量显著下调(P<0.01)。与模型组相比,治疗膜性肾病的中药组合物高剂量+环孢素组及环孢素组Nephrin的mRNA表达量均显著上调(P<0.01);治疗膜性肾病的中药组合物高剂量组Nephrin的mRNA表达明显上调(P<0.05);治疗膜性肾病的中药组合物高剂量组与环孢素组相比无明显差异(P>0.05),实验结果见图6,表5。
与空白组相比,模型组synaptopodin的mRNA表达量均显著下调。与模型组相比,治疗膜性肾病的中药组合物中剂量组、治疗膜性肾病的中药组合物高剂量组、治疗膜性肾病的中药组合物高剂量+环孢素组及环孢素组synaptopodin的mRNA表达量显著上调(P<0.01),以治疗膜性肾病的中药组合物高剂量+环孢素组升高最为明显;治疗膜性肾病的中药组合物高剂量组与环孢素组相比无明显差异(P>0.05)实验结果见图6,表5。
与空白组相比,模型组CD2AP的mRNA表达量均显著下调(P<0.01)。与模型组相比,治疗膜性肾病的中药组合物高剂量+环孢素组及环孢素组CD2AP的mRNA表达量均显著上调(P<0.01);治疗膜性肾病的中药组合物高剂量组CD2AP的mRNA表达明显上调(P<0.05),实验结果见图6,表5。
与空白组相比,模型组desmin的mRNA表达量显著升高(P<0.01)。与模型组相比,治疗膜性肾病的中药组合物高剂量组、治疗膜性肾病的中药组合物高剂量+环孢素组及环孢素组desmin的mRNA表达量均显著下调(P<0.01);治疗膜性肾病的中药组合物中剂量组desmin的mRNA表达明显下调(P<0.05);治疗膜性肾病的中药组合物高剂量组与环孢素组相比无明显差异(P>0.05),实验结果见图6,表5。
与空白组相比,模型组Podocin的mRNA表达量均显著下调(P<0.01)。与模型组相比,治疗膜性肾病的中药组合物高剂量组、治疗膜性肾病的中药组合物高剂量+环孢素组及环孢素组CD2AP的mRNA表达量均显著上调(P<0.01);治疗膜性肾病的中药组合物中剂量组Podocin的mRNA表达明显上调(P<0.05);治疗膜性肾病的中药组合物高剂量组与环孢素组相比无明显差异(P>0.05),实验结果见图6,表5。
表5大鼠肾组织足细胞相关mRNA表达/>
与空白组相比:**P<0.01;与模型组相比:##P<0.01,#P<0.05;与环孢素组相比:●P>0.05。4.10治疗膜性肾病的中药组合物对cBSA大鼠肾小球足细胞自噬及凋亡的影响:
WB检测大鼠肾小球足细胞自噬与凋亡相关蛋白表达水平的变化。结果显示,与空白组相比,模型组大鼠肾组织P62水平显著升高(P<0.01)。与模型组相比,治疗膜性肾病的中药组合物高剂量组、治疗膜性肾病的中药组合物高剂量+环孢素组及环孢素组大鼠肾组织P62水平显著降低(P<0.01)以治疗膜性肾病的中药组合物高剂量+环孢素组降低最为明显,治疗膜性肾病的中药组合物中剂量组明显降低(P<0.05);治疗膜性肾病的中药组合物低剂量组P62水平虽有降低,但差异无统计学意义(P>0.05);治疗膜性肾病的中药组合物中、高剂量组与环孢素组相比差异明显(P<0.05),实验结果见图6,表6。
与空白组相比,模型组大鼠肾组织Beclin-1水平显著降低(P<0.01)。与模型组相比,各治疗组大鼠肾组织Beclin-1水平均显著升高(P<0.01)以治疗膜性肾病的中药组合物高剂量+环孢素组升高最为明显;治疗膜性肾病的中药组合物中、高剂量组与环孢素组相比无明显差异(P>0.05),见图6,表6。
与空白组相比,模型组大鼠肾组织Caspase-3水平显著升高(P<0.01)。与模型组相比,治疗膜性肾病的中药组合物中剂量、治疗膜性肾病的中药组合物高剂量组、治疗膜性肾病的中药组合物高剂量+环孢素组及环孢素组大鼠肾组织Caspase-3水平显著降低(P<0.01)以治疗膜性肾病的中药组合物高剂量+环孢素组降低最为明显,治疗膜性肾病的中药组合物低剂量组明显降低(P<0.05);治疗膜性肾病的中药组合物中、高剂量组与环孢素组相比无明显差异(P>0.05),实验结果见图6,表6。
与空白组相比,模型组大鼠肾组织Bax水平显著升高(P<0.01)。与模型组相比,治疗膜性肾病的中药组合物中剂量、治疗膜性肾病的中药组合物高剂量组、治疗膜性肾病的中药组合物高剂量+环孢素组及环孢素组大鼠肾组织Bax水平显著降低(P<0.01)以治疗膜性肾病的中药组合物高剂量+环孢素组降低最为明显,治疗膜性肾病的中药组合物低剂量组明显降低(P<0.05);治疗膜性肾病的中药组合物中、高剂量组与环孢素组相比差异明显(P<0.05),实验结果见图6,表6。
与空白组相比,模型组大鼠肾组织Bcl2水平显著降低(P<0.01)。与模型组相比,治疗膜性肾病的中药组合物中剂量、治疗膜性肾病的中药组合物高剂量组、治疗膜性肾病的中药组合物高剂量+环孢素组及环孢素组大鼠肾组织Bcl2水平显著升高(P<0.01)以治疗膜性肾病的中药组合物高剂量+环孢素组降低最为明显,治疗膜性肾病的中药组合物低剂量组明显升高(P<0.05);治疗膜性肾病的中药组合物各剂量组与环孢素组相比无明显差异(P>0.05),实验结果见图6,表6。
与空白组相比,模型组大鼠肾组织LC3水平显著降低(P<0.01)。与模型组相比,治疗膜性肾病的中药组合物中剂量、治疗膜性肾病的中药组合物高剂量组、治疗膜性肾病的中药组合物高剂量+环孢素组及环孢素组大鼠肾组织LC3水平显著升高(P<0.01)以治疗膜性肾病的中药组合物高剂量+环孢素组降低最为明显,治疗膜性肾病的中药组合物低剂量组明显升高(P<0.05);治疗膜性肾病的中药组合物中、高剂量组与环孢素组相比无明显差异(P>0.05),实验结果见图6,表6。
表6大鼠肾组织自噬及凋亡相关蛋白表达
与空白组相比:**P<0.01;与模型组相比:##P<0.01,#P<0.05,△P>0.05;与环孢素组相比:●P>0.05,○P<0.05。
PCR结果显示,与Control组相比,模型组Beclin-1的mRNA表达量显著下调(P<0.01)。与模型组相比,治疗膜性肾病的中药组合物高剂量组、治疗膜性肾病的中药组合物高剂量+环孢素组及环孢素组Beclin-1的mRNA表达量均显著上调(P<0.01);治疗膜性肾病的中药组合物低、中、高剂量组与CsA组相比无明显差异(P>0.05),实验结果见图6,表7。
与Control组相比,模型组Caspase-3的mRNA表达量显著上调。与模型组相比,治疗膜性肾病的中药组合物中剂量组、治疗膜性肾病的中药组合物高剂量组、治疗膜性肾病的中药组合物高剂量+环孢素组及环孢素组Caspase-3的mRNA表达量显著下调(P<0.01),以治疗膜性肾病的中药组合物高剂量+环孢素组下降最为明显;治疗膜性肾病的中药组合物高剂量组与环孢素组相比无明显差异(P>0.05),实验结果见图6和表7。
与Control组相比,模型组Bax的mRNA表达量均显著上调(P<0.01)。与模型组相比,治疗膜性肾病的中药组合物各剂量组、治疗膜性肾病的中药组合物高剂量+环孢素组及环孢素组Bax的mRNA表达量均显著下调(P<0.01);治疗膜性肾病的中药组合物高剂量组与环孢素组相比无明显差异(P>0.05),实验结果见图6,表7。
与Control组相比,模型组Bcl2的mRNA表达量显著下调(P<0.01)。与模型组相比,治疗膜性肾病的中药组合物高剂量组、治疗膜性肾病的中药组合物高剂量+环孢素组及环孢素组Bcl2的mRNA表达量均显著上调(P<0.01);治疗膜性肾病的中药组合物低剂量组及治疗膜性肾病的中药组合物中剂量组Bcl2的mRNA表达明显上调(P<0.05);治疗膜性肾病的中药组合物各剂量组与CsA组相比均无明显差异(P>0.05),实验结果见图6,表7。
与Control组相比,模型组LC3的mRNA表达量均显著下调(P<0.01)。与模型组相比,治疗膜性肾病的中药组合物高剂量组、治疗膜性肾病的中药组合物高剂量+环孢素组及环孢素组LC3的mRNA表达量均显著上调(P<0.01);治疗膜性肾病的中药组合物中剂量组及治疗膜性肾病的中药组合物高剂量组与环孢素组相比无明显差异(P>0.05),实验结果见图6表7
表7大鼠肾组织自噬及凋亡相关蛋白的mRNA表达
注:与Control组相比:**P<0.01;与MN组相比:##P<0.01,#P<0.05,△P>0.05;与CsA组相比:●P>0.05。
三、临床试验:
临床试验用药:采用实施例9中的中药组合物配方组成,水煎服,日一付,2次/日。
1研究对象来源:天津中医药大学第一附属医院杨洪涛膜性肾病专病门诊2017年1月1日-2019年12月31日经肾穿刺活检病理诊断确诊为膜性肾病的就诊患者,且均有完善的实验室检查、治疗方案(稳定就诊至少8个月)、病理报告、中医辨证论治方剂等相关资料。
2纳入标准:(1)患者年龄分布于14-75岁,性别不限;(2)符合特发性膜性肾病的西医诊断标准;(3)确诊特发性膜性肾病至初诊时间<1年;(4)起始治疗前未应用免疫抑制剂治疗;(5)确诊时血肌酐<135umol/L。
3排除标准:(1)继发性膜性肾病;(2)进展性膜性肾病(肾功能进行性减退;肾活检见坏死性毛细血管炎和>50%大新月体形成),伴有其他肾脏疾病者;(3)存在其他风湿免疫性疾病指标异常者;(4)有活动期乙型肝炎及持续肝功能异常者;(5)患有恶性肿瘤病史、HIV感染史、精神病史、急性中枢神经系统疾病、严重胃肠道疾病者;(6)重症感染、肾脏或心脏衰竭等严重并发症;(7)智力缺陷或精神病患者;(8)妊娠及哺乳期妇女。
4研究方法
4.1信息采集:从天津中医药大学第一附属医院东华数字医疗信息平台导出符合研究对象的电子病历信息进行信息采集、录入。内容包括姓名、性别、年龄、就诊时间、疾病诊断、病理分型、中医证型、治法、方药、剂量等。
4.2观察指标:患者治疗后3个月、6个月的24小时尿蛋白定量、中医证候积分。
5研究结果
5.1一般情况:共纳入41例患者,其中男性31例,女性10例。年龄最大者75岁,最小者19岁,平均年龄45.34±14.83岁。
5.2 24小时尿蛋白定量编号情况:经秩和检验,与治疗前相比,治疗后3个月、6个月的中医证候积分显著降低(P<0.01),具体结果见表8。
表8
中医证候积分(n=41) | Z | P | |
治疗前 | 18.00(16.500,19.000)** | ||
治疗后3个月 | 9.15±3.038** | -5.588 | 0.000 |
治疗后6个月 | 6.15±4.419** | -5.583 | 0.000 |
5.3中医证候积分变化情况:经秩和检验,与治疗前相比,治疗后3个月、6个月的中医证候积分显著降低(P<0.01),具体结果见表9。
表9
24小时尿蛋白定量(n=41) | Z | P | |
治疗前 | 5.38(3.725,7.970)** | ||
治疗后3个月 | 3.08(1.545,4.150)** | -5.112 | 0.000 |
治疗后6个月 | 2.14(0.705,4.405)** | -5.345 | 0.000 |
5.4疾病疗效情况:治疗后3个月时完全缓解1例,部分缓解15例,无反应25例,完全缓解率2.44%,部分缓解率36.59%,具体结果见表3;治疗后6个月时完全缓解5例,部分缓解23例,无反应13例,完全缓解率12.20%,部分缓解率56.10%,具体结果见表10和表11。
表10
疾病疗效情况(n=41) | |||
完全缓解 | 部分缓解 | 无反应 | |
治疗后3个月 | 1 | 15 | 25 |
治疗后6个月 | 5 | 23 | 13 |
表11
疾病疗效情况(n=41) | ||
完全缓解率 | 部分缓解率 | |
治疗后3个月 | 2.44% | 36.59% |
治疗后6个月 | 12.20% | 56.10% |
虽然,上文中已经用一般性说明及具体实施例对本发明作了详尽的描述,但在本发明基础上,可以对之作一些修改或改进,这对本领域技术人员而言是显而易见的。因此,在不偏离本发明精神的基础上所做的这些修改或改进,均属于本发明要求保护的范围。
Claims (10)
1.一种治疗膜性肾病的中药组合物,其特征在于,所述中药组合物由以下重量份的中药原料药组成:生黄芪10~120份,白术10~60份,枸杞10~60份,杜仲10~60份,蝉蜕5~30份,青风藤10~60份,鬼箭羽10~75份,穿山龙10~75份,败酱草10~60份,金樱子10~75份,车前子10~30份,五味子10~75份,土鳖虫10~30份,当归10~60份。
2.如权利要求1所述的治疗膜性肾病的中药组合物,其特征在于,所述中药组合物由以下重量份的中药原料药组成:生黄芪20-30份、白术10-15份、枸杞15-25份、杜仲15-20份、蝉蜕5-10份、青风藤30-40份、鬼箭羽15-20份、穿山龙15-20份、败酱草20-30份、金樱子30-40份、车前子10-15份、五味子15-20份、土鳖虫20-25份、当归10-30份。
3.如权利要求1所述的治疗膜性肾病的中药组合物,其特征在于,所述中药组合物由以下重量份的中药原料药组成:生黄芪30份、白术15份、枸杞15份、杜仲15份、蝉蜕10份、青风藤30份、鬼箭羽20份、穿山龙20份、败酱草30份、金樱子30份、车前子15份、五味子20份、土鳖虫20份、当归10份;
或所述中药组合物由以下重量份的中药原料药组成:生黄芪20份、白术10份、枸杞15份、杜仲15份、蝉蜕5份、青风藤30份、鬼箭羽15份、穿山龙15份、败酱草20份、金樱子30份、车前子10份、五味子15份、土鳖虫20份、当归10份。
4.如权利要求1~3任意一项所述的治疗膜性肾病的中药组合物,其特征在于,所述中药组合物还包括药学上可接受的辅料。
5.如权利要求4所述的治疗膜性肾病的中药组合物,其特征在于,所述中药组合物为临床上可接受的给药剂型。
6.如权利要求5所述的治疗膜性肾病的中药组合物,其特征在于,所述给药剂型为胃肠道给药制剂,所述胃肠道给药制剂包括片剂、丸剂、散剂、胶囊剂、颗粒剂、口服液或者膏剂。
7.一种如权利要求1~3任意一项所述治疗膜性肾病的中药组合物的制备方法,其特征在于,所述中药原料药的制备包括以下步骤:将各所述中药材混合均匀后碎成粉末,将所得粉末混合均匀制得;
或所述中药原料药的制备包括以下步骤:将各所述中药材均匀混合,用溶剂提取混合均匀的中药材,制得中药提取液;将所制得的中药提取液进行浓缩,制得所述中药原料药;
或所述中药原料药的制备包括以下步骤:将各所述中药材分别用溶剂提取制得中药提取液后,将所制得的中药提取液均匀混合;将混合均匀的中药提取液进行浓缩,制得所述中药原料药。
8.如权利要求7所述的制备方法,其特征在于,所述中药材的提取溶剂为水、乙醇或乙醇水溶液。
9.如权利要求7所述的制备方法,其特征在于,其中,采用溶剂提取中药材时采用的提取方式为煎煮或回流。
10.如权利要求1~3任意一项所述中药组合物在制备预防膜性肾病药物中的应用。
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Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1565520A (zh) * | 2003-06-12 | 2005-01-19 | 曾广财 | 一种治疗肾炎的胶囊 |
CN1626185A (zh) * | 2003-12-08 | 2005-06-15 | 刘立全 | 一种治疗肾脏病的胶囊 |
CN105853678A (zh) * | 2016-04-21 | 2016-08-17 | 陕西中医药大学附属医院 | 一种治疗膜性肾病的中药组合物及其制备方法 |
CN106237011A (zh) * | 2016-08-09 | 2016-12-21 | 山西省中医药研究院 | 一种具有治疗膜性肾病尿蛋白的益气活血消癥中药 |
CN109276685A (zh) * | 2018-10-12 | 2019-01-29 | 天津中医药大学第附属医院 | 预防/治疗前列腺类疾病的中药组合物及其制备方法 |
CN110013470A (zh) * | 2019-03-29 | 2019-07-16 | 江西汇仁药业股份有限公司 | 肾宝片在制备治疗盆腔炎性疾病后遗症药物中的应用 |
CN112206274A (zh) * | 2019-06-24 | 2021-01-12 | 李小军 | 一种治疗精液异常的中药方剂 |
-
2023
- 2023-03-21 CN CN202310278710.XA patent/CN116270870B/zh active Active
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1565520A (zh) * | 2003-06-12 | 2005-01-19 | 曾广财 | 一种治疗肾炎的胶囊 |
CN1626185A (zh) * | 2003-12-08 | 2005-06-15 | 刘立全 | 一种治疗肾脏病的胶囊 |
CN105853678A (zh) * | 2016-04-21 | 2016-08-17 | 陕西中医药大学附属医院 | 一种治疗膜性肾病的中药组合物及其制备方法 |
CN106237011A (zh) * | 2016-08-09 | 2016-12-21 | 山西省中医药研究院 | 一种具有治疗膜性肾病尿蛋白的益气活血消癥中药 |
CN109276685A (zh) * | 2018-10-12 | 2019-01-29 | 天津中医药大学第附属医院 | 预防/治疗前列腺类疾病的中药组合物及其制备方法 |
CN110013470A (zh) * | 2019-03-29 | 2019-07-16 | 江西汇仁药业股份有限公司 | 肾宝片在制备治疗盆腔炎性疾病后遗症药物中的应用 |
CN112206274A (zh) * | 2019-06-24 | 2021-01-12 | 李小军 | 一种治疗精液异常的中药方剂 |
Non-Patent Citations (4)
Title |
---|
基于网络药理学探讨肾苏Ⅲ方改善局灶节段性肾小球硬化大鼠蛋白尿的机制研究;李洁,等;辽宁中医杂志;第47卷(第06期);第190-195、222页 * |
大补元煎合蒙诺治疗慢性肾炎蛋白尿疗效观察;高建东,等;辽宁中医杂志;-;第34卷(第08期);第1076-1077页 * |
尿毒清颗粒治疗糖尿病肾病相关机理研究进展;路文静,等;河南中医;第37卷(第01期);第181-184页 * |
略谈肾炎水肿的治疗体会;杜勉之;江西医药;-(第04期);第32-34、76页 * |
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