基于抗炎和氧化应激角度研究参苓白术颗粒对脾虚湿困溃疡性结肠炎大鼠的作用机制

目的研究参苓白术颗粒对脾虚湿困溃疡性结肠炎(Ulcerative colitis,UC)大鼠血清中炎症因子、抗氧化因子和缺氧相关指标的影响。方法将56只雄性SD大鼠,随机分为正常组,脾虚湿困溃疡性结肠炎模型组,单纯溃疡性结肠炎模型组,参苓白术颗粒低、中、高剂量组(0.472、0.945、1.89 g·kg-1·d-1),阳性药组(柳氮磺吡啶0.2 g·kg-1·d-1),每组8只。以病证结合法复制脾虚湿困模型大鼠,再灌胃5%的葡聚糖硫酸钠(DSS)复制脾虚湿困溃疡性结肠炎模型;单纯溃疡性结肠炎组模型复制期间仅灌胃5%葡聚糖硫酸钠。观察大鼠一般情况及结肠部位损伤情况,计算疾病活动指数(DAI)、体质量、饮食增长率,检测大鼠血清中诱导型一氧化氮合成酶(iNOS)、血清降钙素(PCT)、C反应蛋白(CRP)、髓过氧化物酶(MPO)、超氧化物歧化酶(SOD)、丙二醛(MDA)、红细胞生成素(EPO)、缺氧诱导因子-1α(HIF-1α)含量。结果与正常组比较,脾虚湿困溃疡性结肠炎模型组大鼠疾病活动指数、PCT、CRP、EPO、HIF-1α含量均明显升高(P<0.05,P<0.01),饮食增长率、iNOS、MPO、SOD、MDA含量明显下降(P<0.05,P<0.01);单纯溃疡性结肠炎模型组大鼠疾病活动指数、PCT和CRP含量明显上升(P<0.05,P<0.01),体质量、饮食增长率、iNOS和MPO含量明显下降(P<0.05,P<0.01)。与单纯溃疡性结肠炎模型组比较,脾虚湿困溃疡性结肠炎大鼠疾病活动指数、EPO和HIF-1α含量明显升高(P<0.05,P<0.01),MDA含量明显降低(P<0.01),其它指标无统计学意义;参苓白术颗粒中剂量组能明显降低脾虚湿困溃疡性结肠炎大鼠的疾病活动指数及血清中iNOS、PCT、CRP、EPO含量(P<0.01),提高饮食增长率、SOD及MPO含量(P<0.05,P<0.01)。结论与单纯溃疡性结肠炎模型组比较,脾虚湿困证可加重溃疡性结肠炎大鼠的炎症和缺氧症状。参苓白术颗粒对脾虚湿困溃疡性结肠炎大鼠的结肠损伤有一定治疗作用,可能是通过提高机体的抗炎及抗氧化能力起作用。

Anti-inflammatory and Antioxidant Mechanism of Shenling Baizhu Granules on Experimental Ulcerative Colitis Rats with Dampness Stagnancy Due to Spleen Deficiency

Objective To investigate the effects of Shenling baizhu granules on inflammatory and antioxidant factors in ulcerative colitis rats with dampness stagnancy due to spleen deficiency.Methods Totally 56 male SD rats were divided into 7 groups:normal control group,ulcerative colitis with dampness stagnancy due to spleen deficiency model group(DSSD-UC),pure ulcerative colitis(P-UC)model group,low,medium and high dose of Shenling baizhu granules group(0.472,0.945,1.89 g·kg-1·d-1),positive drug group(salazosulfapyridine 0.2 g·kg-1·d-1),8 mice in each group.Except for the normal control group,the DSSD-UC model group was established by the combination of disease and syndrome,including diet and environment intervention and 5%DSS,while the P-UC model group was only administrated intragastrically with 5%DSS.After 30 days of treatment,the general condition of the rats and the injury of the colon were evaluated.The disease activity index(DAI)score,body weight,and food intake were measured.And the levels of iNOS,PCT,CRP,MPO,SOD,MDA,EPO and HIF-1αin rat serum were determined.Results Compared with the normal control group,DAI score and the contents of PCT,CRP,EPO,HIF-1αin DSSD-UC model group were significantly increased(P<0.05,P<0.01),while food intake and the contents of iNOS,MPO,SOD and MDA were significantly decreased(P<0.05,P<0.01).The DAI score and the contents of PCT,CRP in P-UC group were significantly increased(P<0.05,P<0.01),while body weight,food intake,and the contents of iNOS,MPO were significantly decreased(P<0.05,P<0.01).The DAI score and the contents of EPO,HIF-1αin DSSD-UC model group were significantly higher than that in the P-UC model group,while the MDA content were significantly lower(P<0.05,P<0.01).The medium dose group of Shenling baizhu granules could reduce DAI score,the contentsof iNOS,PCT,CRP,EPO(P<0.01),and increase food intake,the contents of SOD,MPO in DSSD-UC rats serum(P<0.05,P<0.01).Conclusion Compared with the P-UC model group,the syndrome of dampness stagnancy due to spleen deficiency can aggravate the inflammation and hypoxia in UC rats.Shenling baizhu granules has a certain therapeutic effect on colon injury of DSSD-UC rats,which could be related to its anti-inflammatory and antioxidant effects.