CN113425764B - 肉苁蓉总苷及松果菊苷在制备用于预防和治疗酒精性肝损伤伴肠道损伤的药物中的应用 - Google Patents
肉苁蓉总苷及松果菊苷在制备用于预防和治疗酒精性肝损伤伴肠道损伤的药物中的应用 Download PDFInfo
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Abstract
本发明提供了肉苁蓉总苷及松果菊苷在制备用于预防和治疗酒精性肝损伤伴肠道损伤和调节肠道菌群的药物中的应用。药理实验结果表明，在酒精性肝损伤小鼠模型中，肉苁蓉总苷及松果菊苷能够减轻小鼠肝脏组织形态损伤，降低小鼠肝脏的脂质沉积，降低小鼠肝脏谷丙转氨酶(ALT)和谷草转氨酶(AST)含量，减轻小鼠肝脏的氧化损伤，减少内毒素等有害物质对肝脏的损害，同时还能够减轻小鼠小肠组织形态损伤，改善肠壁绒毛完整性，以及调节肠道菌群紊乱。由此可见，本发明具有开发成一种能够同时保护酒精性肝损伤和酒精性肠道损伤的药物的前景，有重要的临床意义和商业价值。
Description
技术领域
本发明属于医药领域，涉及肉苁蓉提取物的一种新用途，具体涉及肉苁蓉总苷及松果菊苷在制备用于预防和治疗酒精性肝损伤伴肠道损伤和调节肠道菌群的药物中的应用。
背景技术
饮酒是造成多种疾病和损伤病症的一个因素，大部分酗酒者会出现组织损伤或器官功能障碍。20％-30％的重度酗酒者患有酒精性脂肪肝炎和肝硬化等酒精性肝病。慢性饮酒会对生长因子、细胞因子和免疫功能产生破坏性影响，通过炎症反应损害机体器官。有报道称，胃肠道可能是酒精介导的器官损伤的重要炎症来源。
酒精性肝病是长期大量饮酒引起的肝脏损伤，长期大量饮酒是该病单一的致病因子，但其发病机制相当复杂，包括酒精的代谢毒性作用、氧化应激、内毒素血症、细胞因子及免疫调节等。酒精及代谢产物积聚会释放大量炎性介质，可破坏肠粘膜上皮细胞的紧密连接，增加肠粘膜上皮对内毒素的通透性，使过多内毒素通过血液循环损伤肝脏。并且，肝脏与肠道在生理结构上经肝门静脉相连，慢性酒精摄入不但会引起肠粘膜通透性升高，还会导致肠道菌群失调(参见，聂娇等，“ECM、MMP-1及TIMP在酒精性肝病伴发肠粘膜损伤中的作用”，山东医药，第52卷第48期，2012年，第1-3页)。可见，酒精性肝损伤和酒精性肠损伤是密切相关的，但是目前对于酒精相关损伤的研究主要集中在酒精性肝病方面，往往忽略了对于酒精性肠损伤等其他方面的研究。
肉苁蓉为列当科肉苁蓉属多年寄生性药用植物，具有极高的药用价值，素有“沙漠人参”的美誉。在我国，肉苁蓉主要分布于新疆、内蒙古地区，甘肃和宁夏也有分布。我国肉苁蓉属植物有4种1变种，分别为荒漠肉苁蓉C.deserticolaY.C.Ma、盐生肉苁蓉C.salsa(C.A.Mey.)G.Beck、白花盐苁蓉C.salsa var.albiflora P.F.Tu et Z.C.Lou、管花肉苁蓉C.tubulosa(Schenk)R.Wight及沙苁蓉C.sinensis G.Beck(屠鹏飞等，中国现代中药，2015,17(4):297-301)。其中，荒漠肉苁蓉和管花肉苁蓉为官方认可作为中药肉苁蓉的基原植物收录入《中国药典》。有研究表明，荒漠肉苁蓉的多糖提取物和苯乙醇苷均能改善酒精诱导的肝损伤模型小鼠的血清和肝脏指标的恢复，提高HepG2细胞的存活，减轻模型动物肝组织中脂肪微泡和坏死细胞，可见荒漠肉苁蓉的多糖提取物和苯乙醇苷对乙醇诱导的慢性肝损伤有显著的保护作用。还有研究表明，富含多糖的荒漠肉苁蓉提取物能够通过激活免疫系统，减少小鼠的炎性粘膜增生和肠内幽门螺杆菌感染，具有预防结直肠癌、肠道炎症的作用(参见，侯蕾等，“肉苁蓉研究进展与产业化现状”，山东农业科学，第52卷第12期，2020年，第133-140页)。
松果菊苷(echinacoside，ECH)是从肉苁蓉中提取的天然化合物，性状为白色结晶粉末。松果菊苷具有很多生物学效应，如神经保护作用、肝脏的保护作用、抗肿瘤、抗凋亡、抗衰老、免疫调节和促进生殖的作用，同时还具有降糖、降脂、促进骨形成以及抗肺动脉高压和预防动脉粥样硬化的作用。此前，有研究表明，松果菊苷能够缓解酒精诱导的氧化应激和肝硬化(参见，ZhiTao,et al.“Echinacoside ameliorates alcohol-inducedoxidative stress and hepaticsteatosis by affecting SREBP1c/FASN pathway viaPPARα”,Food and Chemical Toxicology,Vol 148,2021,111956)。另外，还有研究报道，富含松果菊苷的管花肉苁蓉提取物能够减轻葡聚糖硫酸钠诱导的小鼠结肠炎(参见，YaminJia,et al.“Amelioration of Dextran Sulphate Sodium-Induced Colitis inMice by Echinacoside-EnrichedExtract of Cistanchetubulosa”,PHYTOTHERAPYRESEARCH,Vol 28,2014,110-119)。
从上述对现有技术的综述可知，目前对于肉苁蓉总苷和松果菊苷治疗酒精性肝病的研究均仅是针对单一靶器官肝脏的研究，而没有涉及与酒精性肝损伤相关的其他脏器损伤(特别是与之密切相关的酒精性肠损伤)的研究。此外，对于肉苁蓉总苷和松果菊苷治疗肠病的研究则主要集中在免疫相关的炎症模型上，而这些模型所模拟的肠炎的病理生理机制与酒精性肠损伤是完全不同的。可见，目前尚无同时对肉苁蓉总苷和松果菊苷预防和治疗酒精性肝损伤伴肠道损伤方面的研究，本发明刚好填补了这一技术空白。本发明的研究成果具有开发成一种能够同时保护酒精性肝损伤和酒精性肠道损伤和调节肠道菌群的药物的前景，有重要的临床意义和商业价值。
发明内容
本发明的目的是为了解决现有技术的不足，实现采用现代药物研究方法对天然产物进行开发利用，结合大量药效学实验筛选，提供肉苁蓉总苷及松果菊苷在制备用于预防和治疗酒精性肝损伤伴肠道损伤和调节肠道菌群的药物中的应用。
为达到本发明的目的，本发明采用了如下技术方案：
在第一个方面中，本发明提供了肉苁蓉总苷在制备预防和治疗酒精性肝损伤伴肠道损伤和调节肠道菌群的药物中的应用。
作为可选方式，在上述用途中，所述肉苁蓉总苷是从荒漠肉苁蓉(Cistanchedeserticola)或管花肉苁蓉(Cistanchetubulosa)中提取得到的。
作为可选方式，在上述用途中，所述肉苁蓉总苷的提取方法包括以下步骤：
取肉苁蓉5kg，加8倍量水加热回流，每次2h，共提取三次，合并滤液。滤液减压浓缩至一定体积，加95％乙醇至含醇量达60％，静置过夜；过滤，滤液减压浓缩，过大孔树脂纯化，依次用水和不同浓度的乙醇洗脱，收集其中40％乙醇洗脱液，减压浓缩，干燥，即得肉苁蓉总苷。
作为可选方式，在上述用途中，所述肉苁蓉总苷中包含松果菊苷以及管花苷A、毛蕊花糖苷、异毛蕊花糖苷、2′-乙酰基毛蕊花糖苷或8-表马钱子酸的一种或多种，上述各成分的含量以重量百分比计分别为8-20％、0.2-1.0％、2-10％、1-10％、1-10％和1-10％。
在第二个方面中，本发明提供了松果菊苷在制备预防和治疗酒精性肝损伤伴肠道损伤和调节肠道菌群的药物中的应用。
作为可选方式，在上述用途中，在酒精性肝损伤小鼠模型中，所述肉苁蓉总苷和松果菊苷能够减轻小鼠肝脏组织形态损伤，降低小鼠肝脏的脂质沉积，降低小鼠肝脏谷丙转氨酶(ALT)和谷草转氨酶(AST)含量，减轻小鼠肝脏的氧化损伤，减少内毒素等有害物质对肝脏的损害，同时还能够减轻小鼠小肠组织形态损伤，改善肠壁绒毛完整性，以及调节肠道菌群紊乱。
在第三个方面，本发明提供了一种预防和治疗酒精性肝损伤伴肠道损伤和调节肠道菌群的药物制剂，所述药物制剂包含上述第一个方面和第二个方面所述的药物，以及药学上可接受的载体。
作为可选方式，在上述药物制剂中，所述药物制剂还包含其他临床上常用的治疗酒精性肝损伤的药物。例如，但不限于，五味子，葛根素、水飞蓟素、还原性谷胱甘肽、谷氨酰胺或者维生素D等。
作为可选方式，在上述药物制剂中，所述其他治疗酒精性肝损伤的药物为水飞蓟素，且上述第一个方面或第二个方面所述的药物与水飞蓟素的重量比为5：1-1：5。
优选地，上述第一个方面或第二个方面所述的药物为松果菊苷，所述其他治疗酒精性肝损伤的药物为水飞蓟素，且松果菊苷与水飞蓟素的重量比为4：1。
作为可选方式，在上述药物制剂中，所述药物制剂为口服剂型。
作为可选方式，在上述药物制剂中，所述口服剂型为胶囊剂、片剂、颗粒剂或口服液。优选为片剂或胶囊剂。
所述药学上可接受的载体是指药物制剂领域常规的药物载体，选自填充剂、粘合剂、崩解剂、润滑剂、助悬剂、润湿剂、色素、矫味剂、溶剂、表面活性剂中的一种或几种。
本发明所述填充剂包括但不限于淀粉、微晶纤维素、蔗糖、糊精、乳糖、糖粉、葡萄糖等；所述润滑剂包括但不限于硬脂酸镁、硬脂酸、氯化钠、油酸钠、月桂醇硫酸钠、泊洛沙姆等；所述粘合剂包括但不限于水、乙醇、淀粉浆、糖浆、羟丙基甲基纤维素、羧甲基纤维素钠、海藻酸钠、聚乙烯吡咯烷酮等；所述崩解剂包括但不限于淀粉泡腾混合物即碳酸氢钠和枸橼酸、酒石酸、低取代羟丙基纤维素等；所述助悬剂包括但不限于多糖如金合欢胶、琼脂、藻酸、纤维素醚和羧甲基甲壳酯等；所述溶剂包括但不限于水、平衡的盐溶液等。
可以将所述药物组合物制成各种固体口服制剂、液体口服制剂等。药剂学可接受的口服剂固体制剂有：普通片剂、分散片、肠溶片、颗粒剂、胶囊剂、滴丸、散剂等，口服液体制剂有口服液、乳剂等。上述各种剂型可以根据药物制剂领域的常规工艺制备而成。
本发明中使用的肉苁蓉总苷及松果菊苷可以采样本发明所述的提取分离方法或文献中报道的其他生物提出方法从肉苁蓉中提取分离得到，也可以购自市售产品。
在上文所述的医药用途中，对于肉苁蓉总苷及松果菊苷的给药时间、给药次数和给药频率等等，需要根据病情的具体诊断结果而定，这在本领域技术人员掌握的技术范围之内。
为了更好地理解本发明的实质，在下文具体实施方式部分用药效学实验及其结果来进一步说明肉苁蓉总苷及松果菊苷在制药领域中的新用途。
本发明相对于现有技术，具有以下有益效果：
本发明结合我国在天然产物研究方面的优势，筛选出肉苁蓉总苷及松果菊苷在预防和治疗酒精性肝损伤伴肠道损伤和调节肠道菌群方面的新用途。在酒精性肝损伤小鼠模型中，在酒精性肝损伤小鼠模型中，所述肉苁蓉总苷和松果菊苷能够减轻小鼠肝脏组织形态损伤，降低小鼠肝脏的脂质沉积，降低小鼠肝脏谷丙转氨酶(ALT)和谷草转氨酶(AST)含量，减轻小鼠肝脏的氧化损伤，减少内毒素等有害物质对肝脏的损害，同时还能够减轻小鼠小肠组织形态损伤，改善肠壁绒毛完整性，以及调节肠道菌群紊乱。
值得一提的是，本发明人在对松果菊苷与其他临床上常用的治疗酒精性肝损伤的药物联用预防和治疗酒精性肝损伤伴肠道损伤和调节肠道菌群方面的作用进行研究后，发现了松果菊苷和水飞蓟素在预防和治疗酒精性肝损伤伴肠损伤方面产生了明显的协同作用，尤其在特定重量比的条件下两者协同作用最佳，从而在应用中可以显著降低这两者的给药剂量，减少相关毒副作用。
由此可见，本发明具有开发成一种能够同时保护酒精性肝损伤和酒精性肠道损伤的药物的前景，有重要的临床意义和商业价值。
附图说明
图1：TGs(400mg/kg)能够改善酒精性肝损伤小鼠肝脏组织形态损伤。n＝5，比例尺＝100μm。
图2：TGs抑制酒精性肝损伤小鼠肝脏脂质沉积。A：油红O染色，B：脂质沉积数据统计。与NOR比较，*P<0.05，与MOD比较，#P<0.05，n＝5，比例尺＝100μm。
图3：TGs能够降低酒精性肝损伤小鼠肝脏ALT、AST含量。与NOR比较，*P<0.05，与MOD比较，#P<0.05，n＝5。
图4：TGs能够改善酒精性肝损伤小鼠小肠组织形态。n＝5，比例尺＝100μm。
图5：TGs能够降低酒精性肝损伤小鼠小肠壁PV1蛋白表达。A：PV1蛋白免疫荧光染色，B：PV1蛋白表达量化统计，与NOR比较，*P<0.01，与MOD比较，#P<0.05，n＝3，比例尺＝100μm。
图6：TGs能够显著改善酒精性肝损伤小鼠血清ET、DAO、D-LA、LPS含量。与NOR比较，*P<0.05；与MOD比较，#P<0.05，n＝5。
图7：TGs能够增强酒精性肝损伤小鼠肝脏组织CAT，GSH-Px和SOD活性及减少MDA含量。与NOR比较，*P<0.05；与MOD比较，#P<0.05，n＝5。
图8：TGs激活酒精性肝损伤小鼠肝脏组织Nrf-2/Keap-1信号通路。A：Nrf-2蛋白免疫荧光染色及入核率统计，比例尺＝50μm，B：Keap-1蛋白免疫荧光染色及表达量化统计，比例尺＝100μm。与NOR比较，*P<0.01，与MOD比较，#P<0.05，n＝5。
图9：ECH能够改善酒精性肝损伤小鼠肝脏组织形态损伤。n＝5，比例尺＝100μm。
图10：ECH能够降低酒精性肝损伤小鼠肝脏脂质沉积。n＝5，比例尺＝200μm。
图11：ECH能够降低酒精性肝损伤小鼠肝脏ALT、AST含量。与NOR比较，*P<0.05，与MOD比较，#P<0.05，n＝5。
图12：ECH能够增强酒精性肝损伤小鼠肝脏组织CAT，GSH-Px和SOD活性及减少MDA含量。与NOR比较，*P<0.05；与MOD比较，#P<0.05，n＝5。
图13：ECH能够改善酒精性肝损伤小鼠小肠组织形态。n＝5，比例尺＝100μm。
图14：ECH能够改善肠壁绒毛完整性。
图15：ECH能够降低酒精性肝损伤小鼠小肠壁PV1蛋白表达。A-F分别为：NOR、MOD、ECH50、ECH100、ECH200组，与NOR比较，*P<0.01，与MOD比较，#P<0.05，n＝3，比例尺＝100μm。
具体实施方式
下面参照具体的实施例对本发明做进一步说明。应当理解，此处所描述的具体实施例仅用于解释本发明，并不用于限定本发明的范围。
实施例中未注明具体技术或条件者，按照本领域内的文献所描述的技术或条件，或者按照产品说明书进行。所用试剂或仪器未注明生产厂商者，均为可通过正规渠道购买得到的常规产品。
下面实施例中的实验方法，如无特殊说明，均为常规方法。下述实施例中所用的试验材料，如无特殊说明，均为市售产品。
除非另外说明，否则本发明中涉及的百分比和份数均为重量百分比和重量份数。
实施例1：肉苁蓉总苷、肉苁蓉总多糖和肉苁蓉总寡糖的提取方法
取肉苁蓉5kg，加8倍量水加热回流，每次2h，共提取三次，合并滤液。滤液减压浓缩至一定体积，加95％乙醇至含醇量达60％，低温沉淀12h，滤过，沉淀即为肉苁蓉总多糖；静置过夜；过滤，滤液减压浓缩，过大孔树脂纯化，依次用水和不同浓度的乙醇洗脱。收集水洗脱液，减压浓缩至稠膏，即得肉苁蓉总寡糖；收集其中40％乙醇洗脱液，减压浓缩，干燥，即得肉苁蓉总苷。
肉苁蓉总苷主要含苯乙醇苷类和环烯醚萜苷类。采用高效液相色谱法对其松果菊苷、管花苷A、毛蕊花糖苷、异毛蕊花糖苷、2’-乙酰基毛蕊花糖苷、8-表马钱子酸的含量进行测定，分别为16.31％、0.41％、4.17％、2.27％、1.20％、2.78％；采用紫外分光光度法，分别以松果菊苷和8-表马钱子酸为对照，对其总苯乙醇苷和总环烯醚萜苷进行了含量测定。结果表明，本品以干燥品计，含总苯乙醇苷以松果菊苷计为43.21％，含总环烯醚萜苷以8-表马钱子酸计为32.18％。
实施例2：肉苁蓉总苷和松果菊苷保护酒精性肝损伤伴肠道损伤的药效学研究2.1肉苁蓉总苷保护酒精性肝损伤伴肠道损伤的药效学研究结果
将30只雄性健康昆明小鼠随机分为正常组(NOR)、模型组(MOD)、肉苁蓉总苷组(TGs，400mg/kg)，肉苁蓉多糖组(PSs，400mg/kg)，与肉苁蓉寡糖组(OSs，400mg/kg)六组，每组10只。灌胃红星二锅头建立酒精性肝损伤模型，造模7天后分别灌胃给与生理盐水与药物，连续给药14天。
HE染色(图1)显示，NOR组的肝脏组织细胞形态正常、排列整齐、结构完整；MOD组结构紊乱，细胞排列不规则，细胞间隙疏松，细胞界限不清；TGs干预后细胞形态改变明显好于MOD组，细胞数量较MOD组多，说明肉苁蓉总苷具有肝保护作用。
油红O染色(图2)显示，NOR组有少量的脂质沉积，而MOD组脂质沉积明显增加；与MOD组相比，TGs干预后脂质沉积明显减少，说明肉苁蓉总苷能够减轻酒精性肝损伤小鼠肝脏脂质沉积。
生化指标检测(图3)显示，与NOR组相比，MOD组ALT和AST水平明显增加；与MOD组相比，TGs组ALT和AST水平明显降低；说明肉苁蓉总苷抑制肝脏损伤，具有肝保护作用。
小肠HE染色结果(图4)显示，NOR组小肠组织细胞形态正常，绒毛排列整齐，肠壁均匀，细胞结构完整，细胞间隙致密；MOD组结构紊乱，绒毛排列不规则，断裂状，肠壁变薄；TGs干预后细胞形态得到明显改变，肠壁增厚，说明肉苁蓉总苷对肠壁和绒毛完整性具有保护作用。
质膜相关蛋白1(PV1)是一种与内皮横膈膜相关的整合膜蛋白，可作为肠血管屏障遭到破坏的标志物。免疫荧光染色结果(图5)可见，与NOR组相比，MOD组小肠壁中PV1蛋白表达水平显著增加；与MOD组相比，TGs组PV1蛋白表达量明显降低，说明肉苁蓉总苷能够促进小肠壁修复。
酒精可破坏肠道完整性，使肠道内细菌代谢产物进入体循环，通过门静脉到达肝脏，进而加重肝脏损伤。图6显示，肉苁蓉总苷可以通过降低酒精在肠道的通透性，进而降低血液中内毒素、脂多糖、二胺氧化酶和D-乳酸(D-LA)含量,防止有害物质通过门静脉进入肝脏，进而起到肝保护的作用。
对样本的氧化应激因子检测结果(图7)显示，与NOR组相比，MOD组超氧化物歧化酶(SOD)，过氧化氢酶(CAT)，谷胱甘肽过氧化物酶(GSH-Px)活性显著降低，MDA含量显著升高；TGs干预后SOD，CAT，GSH-Px活性显著升高，MDA含量显著降低。
在氧化应激条件下，Ke l ch样环氧氯丙烷相关蛋白1/核因子E2相关因子2(Keap-1/Nrf-2)复合物可参与多种抗氧化基因的转录激活，从而提供细胞保护作用。免疫荧光染色结果(图8)可见，与NOR组相比，MOD组肝脏中Nrf-2入核率显著降低；Keap-1蛋白表达水平显著上升；与MOD组相比，TGs组Nrf-2入核率显著增加，Keap-1蛋白表达水平明显降低。
上述结果说明，肉苁蓉总苷可以通过激活Keap-1/Nrf-2信号通路，增加抗氧化酶SOD、CAT和GSH-Px活性，起到肝保护的作用。
2.2松果菊苷保护酒精性肝损伤伴肠道损伤的药效学研究结果
将60只雄性昆明小鼠随机分为正常组(NOR)、模型组(MOD)、阳性药联苯双酯组(BIF，100mg/kg)，松果菊苷低剂量组(ECH 50mg/kg)，松果菊苷中剂量组(ECH 100mg/kg)，以及松果菊苷高剂量组(ECH 200mg/kg)。采用灌胃红星二锅头酒方式造模，造模7天后分别灌胃给与生理盐水及各药物，连续给药14天后取材。
HE染色(图9)结果显示，NOR组肝脏组织细胞形态正常，细胞排列整齐，染色均匀，细胞结构完整，细胞间隙致密；MOD组结构紊乱，细胞排列不规则，细胞间隙疏松，细胞界限不清；ECH干预后各组细胞形态改变明显好于模型组，细胞数量较模型组多，说明松果菊苷具有肝保护作用。
油红O染色(图10)结果显示，NOR组有少量的脂质沉积，而MOD组脂质沉积明显增加；与MOD组相比，ECH(50mg/kg、100mg/kg和200mg/kg)干预后脂质沉积明显减少；说明松果菊苷能够减轻酒精性肝损伤小鼠肝脏脂质沉积。
生化检测结果显示(图11)，与NOR组相比，MOD组ALT和AST水平明显增加；与MOD组相比，ECH组ALT和AST水平明显降低，且呈剂量依赖性，说明松果菊苷能够抑制酒精性肝脏损伤，具有肝保护作用。
氧化应激因子检测结果(图12)显示，与NOR组相比，MOD组SOD，CAT，GSH-Px活性显著降低，MDA含量显著升高，与MOD组相比，ECH(50μmol/L，100μmol/L和200μmol/L)干预后SOD，CAT，GSH-Px活性显著升高，MDA含量显著降低，说明松果菊苷具有显著抗氧化作用。
小肠组织经HE染色后显示(图13)，NOR组小肠组织细胞形态正常，绒毛排列整齐，肠壁均匀，细胞结构完整，细胞间隙致密；MOD组结构紊乱，绒毛排列不规则，断裂状，肠壁变薄；ECH(50mg/kg，100mg/kg和200mg/kg)干预后细胞形态得到明显改变，肠壁增厚，说明松果菊苷能够改善肠壁和绒毛完整性。
电镜结果显示(图14)，NOR组小肠绒毛排列整齐，无断裂，绒毛间隙致密；MOD组绒毛排列不规则，断裂状，绒毛间隙增加；ECH干预后各组绒毛形态明显得到改变，绒毛排列整齐，间隙变小，也证明松果菊苷能够改善肠壁绒毛完整性。
免疫荧光染色结果(图15)可见，与NOR组相比，MOD组小肠壁中PV1蛋白表达水平显著增加；与MOD组相比，ECH各组PV1蛋白表达量明显降低，说明松果菊苷能够促进小肠壁修复。
肠道菌群测序结果显示，酒精性肝损伤小鼠中肠道菌群结构发生明显改变，使拟杆菌门、放线菌门、芽孢杆菌纲、微球菌科、理研菌属、罗斯氏菌属等放线菌门、杆菌纲的丰度降低，厚壁菌门、瘤胃菌科、丁酸弧菌属等的丰度升高，而松果菊苷给药可以逆转这些变化，表明松果菊苷可以调节肠道菌群紊乱。
2.3松果菊苷与其他临床上常用的治疗酒精性肝损伤的药物联用预防和治疗酒精性肝损伤伴肠道损伤的药效学初步评价结果
在上述2.1和2.2部分实验的基础上还做了延伸实验，初步考察了将松果菊苷与其他临床上常用的治疗酒精性肝损伤的药物联用后，其预防和治疗酒精性肝损伤伴肠道损伤的药效。
将120只雄性昆明小鼠随机分为正常组(NOR)、模型组(MOD)、松果菊苷低剂量组(ECH 50mg/kg)、松果菊苷高剂量组(ECH 100mg/kg)、水飞蓟素低剂量组(SLM 12.5mg/kg)、水飞蓟素中剂量组(SLM 25mg/kg)、水飞蓟素高剂量组(SLM 50mg/kg)、联用1组(ECH100mg/kg+SLM 25mg/kg)、联用2组(ECH 50mg/kg+SLM 12.5mg/kg)、联用3组(ECH 50mg/kg+SLM 50mg/kg)、联用4组(ECH 100mg/kg+葛根素25mg/kg)和联用5组(ECH 100mg/kg+还原性谷胱甘肽25mg/kg)。采用灌胃红星二锅头酒方式造模，造模7天后分别灌胃给与生理盐水及各药物，连续给药14天后取材。
肠上皮细胞凋亡抑制情况检测：利用TUNEL细胞凋亡检测试剂盒对小鼠肠上皮细胞的凋亡情况进行检测。操作步骤：脱蜡，蛋白酶消化20min后清洗，加入TUNEL反应混合液，于37℃下封闭30min，加底物显色，苏木素复染、脱水、封片。每组分别随机选取10张切片，每张切片选择10个具有代表性的高倍视野(x400)，计数500个细胞中TUNEL染色的阳性细胞数，采样凋亡抑制指数表示，凋亡抑制指数＝1-(凋亡细胞数/细胞总数)x100％。
协同指数采用金正均q值法进行判定，q值由以下的公式求得：q＝PA+B/(PA+PB-PA×PB)。式中PA、PB和PA+B分别为A药组、B药组和两药联用组治疗率。q＜1说明两药合用后产生拮抗作用；q＞1，说明两药合用后产生协同作用，q＝1说明两药合用后产生相加作用。
具体结果如下：
经单因素方差分析检验，##表示与空白组相比P<0.01；*和**表示与模型组相比，P<0.05和P<0.01。
从上表中的结果可以看出，上述实验中考察的松果菊苷与水飞蓟素的组合均显示出明显的协同作用，并且以松果菊苷和水飞蓟素的重量比4：1的协同作用最佳。
综上所述，药理实验结果表明，在酒精性肝损伤小鼠模型中，在酒精性肝损伤小鼠模型中，所述肉苁蓉总苷和松果菊苷能够减轻小鼠肝脏组织形态损伤，降低小鼠肝脏的脂质沉积，降低小鼠肝脏谷丙转氨酶(ALT)和谷草转氨酶(AST)含量，减轻小鼠肝脏的氧化损伤，减少内毒素等有害物质对肝脏的损害，同时还能够减轻小鼠小肠组织形态损伤，改善肠壁绒毛完整性，以及调节肠道菌群紊乱。
值得一提的是，本发明人在对松果菊苷与其他临床上常用的治疗酒精性肝损伤的药物联用预防和治疗酒精性肝损伤伴肠道损伤方面的作用进行研究后，发现了松果菊苷和水飞蓟素在预防和治疗酒精性肝损伤伴肠损伤方面产生了明显的协同作用，尤其在特定重量比的条件下两者协同作用最佳，从而在应用中可以显著降低这两者的给药剂量，减少相关毒副作用。
由此可见，本发明具有开发成一种能够同时保护酒精性肝损伤和酒精性肠道损伤和调节肠道菌群的药物的前景，有重要的临床意义和商业价值。
显然，本领域的技术人员可以对本发明进行各种改动和变型而不脱离本发明的精神和范围。这样，倘若本发明的这些修改和变型属于本发明权利要求及其等同技术的范围之内，则本发明也意图包含这些改动和变型在内。
Claims (3)
1.一种预防和治疗酒精性肝损伤伴肠道损伤和调节肠道菌群的药物制剂，其特征在于：所述药物制剂包含药物以及药学上可接受的载体，所述药物由松果菊苷和水飞蓟素组成，所述松果菊苷与所述水飞蓟素的重量比为4：1。
2.根据权利要求1所述的药物制剂，其特征在于：所述药物制剂为口服剂型。
3.根据权利要求2所述的药物制剂，其特征在于：所述口服剂型为胶囊剂、片剂、颗粒剂或口服液。
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101618133A (zh) * | 2008-06-30 | 2010-01-06 | 广州白云山和记黄埔中药有限公司 | 强阳保肾药物在制备防治骨质疏松症药物中的应用 |
-
2021
- 2021-07-16 CN CN202110808780.2A patent/CN113425764B/zh active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101618133A (zh) * | 2008-06-30 | 2010-01-06 | 广州白云山和记黄埔中药有限公司 | 强阳保肾药物在制备防治骨质疏松症药物中的应用 |
Non-Patent Citations (6)
| Title |
|---|
| Echinacoside ameliorates alcohol-induced oxidative stress and hepatic steatosis by affecting SREBP1c/FASN pathway via PPARα;Zhi Tao et.al;《Food and Chemical Toxicology》;20201227;第1-9页，尤其是第1页摘要 * |
| Echinacoside Stimulates Cell Proliferation and Prevents Cell Apoptosis in Intestinal Epithelial MODE-K Cells by Up-Regulation of Transforming Growth Factor-β1 Expression;Yamin Jia et al.;《Journal of Pharmacological Sciences》;20121231;第99-108页，尤其是第99页摘要 * |
| 肉苁蓉总苷对小鼠酒精性肝损伤的保护作用;罗慧英等;《中国临床药理学与治疗学》;20091231;第14卷(第11期);第1225-1228页，尤其是第1225页摘要、右栏第2段 * |
| 肉苁蓉提取物对快速老化模型小鼠SAMP8行为学及肠道菌群的影响;付志飞等;《世界科学技术—中医药现代化》;20191231;第21卷(第6期);第1103-1109 * |
| 肉苁蓉水提取物体外抗氧化及对小鼠肠道菌群紊乱的作用;何梦梦等;《食品研究与开发》;20201231;第41卷(第23期);第44-50页，尤其是第44页摘要，第45页左栏第3段，第47页右栏第4段 * |
| 肉苁蓉润肠通便的药效物质研究;高云佳等;《中国现代中药》;20150430;第17卷(第4期);第307-310、314页，尤其是第308页左栏倒数第1段、右栏第1、3段 * |
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