祛瘀护膜剂调控NLRP3/Caspase-1信号通路对RE模型大鼠食管黏膜修复的影响

Effect of Quyu Humo Paste on the Repair of Esophageal Mucosa in Rats with Reflux Esophagitis by Regulating NLRP3/Caspase-1 Signaling Pathway

    摘要
  • 摘要:
      目的  从食管黏膜屏障修复的角度, 探讨祛瘀护膜剂对反流性食管炎(RE)模型大鼠核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)/天冬氨酸特异性半胱氨酸蛋白酶-1(Caspase-1)信号通路的影响, 揭示祛瘀护膜剂治疗RE的作用机制。
      方法  将大鼠随机分空白组, 模型组, 西药组, 祛瘀护膜剂低、中、高剂量组, 每组10只。除空白组外, 其余5组均使用“4.2 mm幽门夹+2/3胃底结扎术”方法建立RE大鼠模型, 空白组及模型组予淀粉+蒸馏水, 祛瘀护膜剂低、中、高剂量组分别予祛瘀护膜剂0.54、1.62、4.86 g·kg-1, 西药组予铝镁加混悬液, 灌胃给药14 d。第15天采血后处死大鼠并取出食管组织。ELISA法检测大鼠血清Caspase-1、白细胞介素-1β(IL-1β)、白细胞介素-18(IL-18)水平, Western blot法检测食管组织中NLRP3、Caspase-1蛋白表达情况, HE染色光镜下观察食管组织病理变化。
      结果  与空白组比较, 模型组血清Caspase-1、IL-1β、IL-18水平及食管组织中NLRP3、Caspase-1蛋白表达量显著升高(P < 0.001)。与模型组比较, 西药组及祛瘀护膜剂中、高剂量组血清Caspase-1、IL-1β、IL-18水平及食管组织中NLRP3、Caspase-1蛋白表达量显著下降(P < 0.001)。与西药组比较, 祛瘀护膜剂高剂量组食管组织中NLRP3、Caspase-1蛋白表达量明显下降(P < 0.01), 血清Caspase-1水平显著下降(P < 0.001)。
      结论  祛瘀护膜剂通过抑制NLRP3信号通路的过度激活, 下调Caspase-1的表达, 降低IL-1β、IL-18水平, 拮抗食管炎症反应, 从而改善食管上皮损伤进而修复食管黏膜, 促进大鼠RE的愈合。

     

    Abstract:
      OBJECTIVE  From the perspective of esophageal mucosal barrier repair, to explore the effect of Quyu Humo paste on nucleotide binding oligomeric domain-like receptor protein 3 (NLRP3)/aspartate specific cysteine protease-1 (Caspase-1) signal pathway in rats with reflux esophagitis (RE), and to reveal the mechanism of Quyu Humo paste in the treatment of RE.
      METHODS  Rats were randomly divided into blank group (n=10), model group (n=10), western medicine group (n=10), low dose Quyu Humo paste group (n=10), middle dose Quyu Humo paste group (n=10) and high dose Quyu Humo paste group (n=10). Except the blank group, the RE rat model was established by "4.2 mm pyloric clip+2/3 gastric fundus ligation" in the other 5 groups. The rats in the blank group and model group were given starch+distilled water, each doses of Quyu Humo paste groups were treated with Quyu Humo paste of 0.54, 1.62, 4.86 g·kg-1, respectively, and western medicine group were given aluminum and magnesium plus suspension for 14 d. On the 15th day, the rats were killed and the esophageal tissues were taken out. The contents of Caspase-1, IL-1β and IL-18 in serum were detected by ELISA method, the protein expressions of NLRP3 and Caspase-1 in esophageal tissue were detected by Western blot, and the pathological changes of esophageal tissue were observed under light microscope with HE staining.
      RESULTS  The protein expressions of Caspase-1, IL-1β, IL-18 in serum and NLRP3 and Caspase-1 in esophageal tissue in the model group were significantly higher than those in the blank group (P < 0.001). Compared with the model group, the contents of Caspase-1, IL-1β, IL-18 in serum and the protein expressions of NLRP3 and Caspase-1 in esophageal tissue decreased significantly in western medicine group, middle and high dose Quyu Humo paste groups (P < 0.001). Compared with the western medicine group, the protein expressions of NLRP3 and Caspase-1 in esophageal tissue and Caspase-1 in serum significantly decreased in the high dose Quyu Humo paste group (P < 0.01, P < 0.001).
      CONCLUSION  Quyu Humo paste can improve the injury of esophageal epithelium, repair esophageal mucosa and promote the healing of reflux esophagitis in rats by inhibiting the excessive activation of NLRP3 signal pathway, down-regulating the expression of Caspase-1, reducing the levels of IL-1β and IL-18, and antagonizing esophageal inflammation.

     

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