中文题名: | 葛根素pH响应性生物黏附微球的制备及对乙醇诱导大鼠急性胃黏膜损伤的保护作用研究 |
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学科代码: | 100800 |
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学生类型: | 硕士 |
学位: | 医学硕士 |
学位年度: | 2015 |
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研究方向: | 中药资源保护与利用 |
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提交日期: | 2015-06-29 |
答辩日期: | 2015-05-19 |
外文题名: | PuerarinMucoadhesiveMicroparticlesforGastroretentiveDelivery:Preparation,BiodistributionandTargetingEvaluation |
中文摘要: |
葛根素是存在于大量植物的一种重要黄酮。葛根素联合其他药物用药可以治疗应激性胃黏膜损伤及十二指肠溃疡。本文根据中医治证特点,设计制备了海藻酸钠-壳聚糖载葛根素粘附微球。并且利用差示扫描量热法(DSC)和傅里叶变换红外光谱(IR)分析了该载体的结构特点及成型机理。同时以模拟胃液为释放介质研究微球的体外释放性能,并借助体内外粘附实验考察了该微球剂型的生物粘附性。研究结果显示葛根素粘附微球在12h内可持续释放;离体胃生物粘附测定实验结果表明,经过模拟胃液冲洗后,葛根素粘附微球在胃内仍有大量剩余,滞留百分率达93.50%,体内荧光示踪实验结果显示,给药8h后仍有少量微球附着在胃壁,体内外实验证实微球对胃肠壁具有较好的黏膜粘附性。此外,以无水乙醇灌胃致大鼠急性胃粘膜损伤模型,研究了葛根素粘附微球的胃粘膜损伤的保护作用。在乙醇致胃溃疡大鼠模型中,葛根素粘附微球各剂量组能显著降低溃疡指数,显示了较高的溃疡抑制百分率,以保护胃黏膜。通过酶联免疫吸附法(ELISA)测定了黏膜组织中的炎性因子分泌表达,葛根素粘附微球能提高作为关键防御因素的前列腺素(PGE2)水平,而下调相关的炎症因子白介素1β(1L-1β)、白介素6(1L-6)和肿瘤坏死因子(TNF-α)的分泌,与模型组相比,具有显著性差异。黏膜组织PAS染色结果也显示给予不同剂量微球后粘膜损伤明显减轻,仅有少数细胞脱落,细胞出血性损伤减轻。各项实验结果综合分析表明,海藻酸钠-壳聚糖载葛根素粘附微球对大鼠胃黏膜损伤具有显著的保护作用。
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外文摘要: |
Puerarin is a major isoflavone found in a number of plants and herbs Increasing evidence suggests that puerarin can protect gastric mucosa from stress-induced injury .We choose Puerarin as the model drug and prepared alginate-chitoan loaded Puerarin microspheres. The interaction between chitosan and alginate was assessed by differential scanning calorimetry (DSC) and conformed by Fourier transform infrared spectroscopy (FT-IR). In vitro release studies demonstrated that Puerarin microspheres keep sustained release in 12h in the simulated gastric fluid. And it was found in vitro adhesion experiment that Puerarin microspheres could adhere strongly to gastric mucous and retain in the gastrointestinal tract, the percentage mucoadhesion was 93.50% after rinsed for a period of time; meanwhile, the result was further confirmed by in vivo mucoadhesive test. At the same time, the gastroprotective effect of the microspheres against ethanol-induced gastric ulcer model in rats was also evaluated in vivo. Chitosan-coated Puerarin microspheres could reduce ulcer index significantly, and showed a higher percentage inhibition; it could also reduce the gastric acidity as well as increase mucus production. The production of relevant proteins was examed by enzyme-linked immunosorbent assay (ELISA). Chitosan-coated Puerarin microspheres could raise prostaglandin E2 (PGE2) level but down-regulate tumor necrosis factor-α (TNF-α) , interleukin1β (1L-1β) and interleukin6 (1L-6)in gastric mucosa. The results of histological evaluation also found that gastric mucosa damages were markedly attenuated, with only slight injury observed in superficial gastric epithelium when pretreated with microspheres. Gastroprotective effects of microspheres might attribute to the anti-inflammatory properties to the gastric mucosa.
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参考文献总数: | 73 |
馆藏号: | 硕1008/1503 |
开放日期: | 2015-06-29 |