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目的探讨双歧三联活菌片(金双歧)防治甲氨蝶呤(MTX)所致Wistar大鼠肠黏膜炎的机制和疗效。方法Wistar大鼠54只随机分为正常对照组(A组)、MTX损伤组(B组)及金双歧干预组(C组)3组。B、C组每天予1次MTX100mg/kg(9g/L盐水稀释成1mL)腹腔注射,C组于注射MTX前2d开始每日早晚2次各喂食金双歧1粒。于造模成功第1、3、5天各处死6只大鼠,采用免疫组织化学法检测大鼠肠黏膜组织中TNF-α表达;ELISA法检测其肠黏膜表面黏液中分泌性IgA(sIgA)表达;对其肠系膜淋巴结进行细菌培养以观察大鼠肠道细菌移位,并在HE染色下观察其小肠组织形态学变化及各组大鼠死亡情况。结果C组大鼠肠黏膜组织形态较B组明显改善,绒毛高度和隐窝深度在第1、3、5天均高于B组(Pa<0.05);上皮细胞中TNF-α表达轻于B组(P<0.05);黏膜表面sIgA水平在第1、3、5天均高于B组(Pa<0.05);肠道细菌移位在第3、5天明显少于B组(Pa<0.05),大鼠病死率明显低于B组(P<0.05)。结论MTX诱发黏膜炎是一个急性损伤过程,双歧杆菌能够显著减轻大鼠肠黏膜炎性反应,缩短病程,为应用微生态制剂治疗化疗过程中所产生的不良反应提供了理论依据。
Objective To investigate the mechanism and efficacy of bifidobacterium triple viable tablet (Jinshuangqi) in the prevention and treatment of intestinal mucositis in methotrexate (MTX) -induced Wistar rats. Methods Fifty-four Wistar rats were randomly divided into three groups: normal control group (A group), MTX injury group (B group) and Jinshuangqi intervention group (C group). Groups B and C were intraperitoneally injected with MTX100mg / kg (9g / L saline diluted to 1mL) once a day, while C group was given 2 doses of Jinshuangqi twice daily morning and evening 2 days before MTX injection. Six rats were sacrificed on the 1st, 3rd, 5th day after successful model establishment. The expression of TNF-α in the intestinal mucosa was detected by immunohistochemical method. The secretory IgA (sIgA) The mesenteric lymph nodes were cultured in order to observe the intestinal bacterial translocation in rats. The morphological changes of small intestine and the death of rats in each group were observed under HE staining. Results The histological changes of intestinal mucosa in group C were significantly improved compared with those in group B, and the villus height and crypt depth were significantly higher than those in group B on the 1st, 3rd and 5th day (P <0.05). The expression of TNF-α in epithelial cells was lighter than that of B (P <0.05). The sIgA level of mucosal surface was higher than that of B group on the 1st, 3rd and 5th day (P <0.05). The intestinal bacterial translocation was less on the 3rd and 5th day than that of the B group ), The mortality in rats was significantly lower than that in group B (P <0.05). Conclusions MTX-induced mucositis is an acute injury process. Bifidobacterium can significantly reduce the inflammatory reaction of intestinal mucosa and shorten the course of the disease in rats, which provides a theoretical basis for the application of probiotics in the treatment of adverse reactions during chemotherapy.