嗜酸乳杆菌对实验性结肠炎小鼠肠黏膜趋化因子RANTES和MCP-1表达的影响

Effect of lactobacillus acidophilus on expressions of chemokines RANTES and MCP-1 in murine intestinal mucosa with experimental ulcerative colitis

目的观察嗜酸乳杆菌对小鼠溃疡性结肠炎(UC)肠黏膜趋化因子RANTES和单核细胞趋化蛋白(MCP-1)表达的影响,了解其治疗UC的效果及其可能的作用机制。方法采用2.5%的葡聚糖硫酸钠(DSS)建立小鼠结肠炎模型。70只BALB/c小鼠随机分为正常组,阴性对照(生理盐水,NS)组,阳性对照(美沙拉嗪)组,模型对照组,嗜酸乳杆菌低剂量(106CFU/ml)、中剂量(107CFU/ml)组、高剂量(108CFU/ml)组。用疾病活动指数(DAI)评分和病理组织学积分检测各干预组的疗效;免疫组织化学法检测结肠组织中趋化因子RANTES和MCP-1蛋白的表达;反转录-聚合酶链反应(RT-PCR)检测结肠组织中RANTES、MCP-1和STAT1基因的表达。结果嗜酸乳杆菌可改善实验性结肠炎小鼠一般情况,降低DAI积分;与模型、阴性对照组相比,RANTES和MCP-1蛋白、基因的表达均下降(P<0.05);转录因子STAT1基因表达也下降(P<0.05)。其效果与美沙拉嗪相当,其中以嗜酸乳杆菌高剂量组效果最佳。结论嗜酸乳杆菌对急性期实验性结肠炎小鼠有治疗作用,疗效与剂量呈正相关;其部分机制可能与通过抑制转录因子STAT1的激活,进而减少结肠黏膜趋化因子RANTES和MCP-1的表达有关。

Objective To investigate the effect of lactobacillus acidophilus on expressions of chemokines RANTES and MCP-1 in murine intestinal mucosa with experimental ulcerative colitis （UC） and its possible mechanism. Methods Dextran sulphate sodium （DSS） was used to induce UC in BALB/c mice. Seventy mice were randomly divided into seven groups as follows： normal control group, negative control group （normal saline, NS group）, positive control group （mesalazine）, model control group, low-dose （106 CFU/ml）, moderate-dose （107 CFU/ml） and high-dose （10s CFU/ml） lactobacillus acidophilus groups. Disease activity index （DAI） and histological injury score were used to assess the efficacy of intervention groups; chemokines RANTES and MCP-1 expression in colonic nmcosa were measured by immunohistochemistry （IHC）; RANTES, MCP-1 and STAT1 mRNA expressions were measured by reverse transcrip- tion polymerase chain reaction （RT-PCR）. Results Lactobacillus acidophilus was shown to improve the general conditions and DAI scores in mice; The protein and mRNA expressions of RANTES and MCP-1 were both decreased （P〈 0.05） in lactobacillus acidophilus intervention groups, compared with model control and negative control groups;The expression of STAT1 at gene level was also decreased （P〈0.05）. Such effect of lactobacillus acidophilus was similar to mesalazine, and was most evidenced in high-dose group. Conclusion Lactobacillus acidophilus had a therapeutic effect for mice with acute UC. The mechanism may be possibly related to the inhibition of transcription factor STAT1 activation, which in turn leads to lowered expression of chemokines RANTES and MCP-1 in colonic mucosa.