摘要
目的：本实验旨在通过肠愈宁对溃疡性结肠炎大鼠S100、CD83、Foxp3及STAT6表达情况的研究,探讨溃疡性结肠炎在发病的过程中可能的发病机制以及肠愈宁对溃疡性结肠炎治疗过程中免疫系统的调节作用。
方法：将成年Wistar大鼠120只,随机分为空白组、模型对照组、中药低剂量组、中药高剂量组、中药正常剂量组、西药对照组。除正常对照组外,其余5组,共100只大鼠采用改良的2,4-二硝基氯苯乙酸复合法制备大鼠UC实验模型。硫化钠在大鼠颈背部脱毛DNCB丙酮液(DNCB2.0g,丙酮100m1)涂于脱毛部皮肤,每天一次,连续14天,于第15天经肛门注入结肠DNCB乙醇(50%)。于第16天在同部位注入乙酸溶液。按人鼠给药剂量体表面积折算公式计算出给药剂量。各治疗组均与造模成功后1周给予药物灌胃空白组、模型组按照10ml/kg·d灌服蒸馏水,每日一次连续4周；中药低剂量组：按每日给予10ml/kg·d的中药灌胃(浓度为0.5g/ml),每日一次；中药高剂量组：按每日给予10ml/kg·d的中药灌胃(浓度为4glml)，每日一次；中药正常剂量组：按每日给予10mllkg·d的中药灌胃(浓度为1g/m1),每日一次。西药对照组：按0.5g/kg.d给予柳氮磺胺毗啶,连续4周。给药4周后观察大鼠结肠粘膜的病理变化,以及药物对S100、CD83、STAT6、Foxp3的表达水平的影响
结果：1.空白组较模型组S100及CD83表达低,而西药组、低剂量组、中剂量组及高剂量组S100及CD83表达较模型组低,较空白组高；西药组、中药中剂量组S100及CD83表达较中药高剂量组与低剂量组均低；与西药组比较,中药中剂量组S100及CD83表达水平下降。2.模型组较空白组Foxp3表达低(P<0.01),而西药组低剂量组、中剂量组及高剂量组Foxp3表达较模型组高,较空白组低,具有统计学差异(P<0.05)；西药组、中药中剂量组Foxp3表达较中药高剂量组与低剂量组均高,具有统计学意义(P<0.05)；与西药组比较,中药中剂量组Foxp3表达水平上升,P<0.05,具有统计学意义。3.空白组较模型组STAT6含量低(P<0.01),而西药组及中剂量组STAT6含量较模型组低,较空白组高,具有统计学差异(P<0.05)；西药组、中药中剂量组STAT6含量较中药高剂量组与低剂量组均低,具有统计学意义(P<0.05)；与西药组比较,中药中剂量组STAT6表达水平高,但P>0.05,差异无统计学意义。
结论：1.UC病变大鼠S100、CD83表达水平明显增高,肠愈宁降低S100、CD83表达水平,可能进而减少了树突状细胞的过表达。2.UC病变大鼠Foxp3的表达水平明显降低,肠愈宁可升高Foxp3的表达水平,且中剂量肠愈宁较柳氮磺胺吡啶的升高作用更为明显,这一作用可能是通过加强调节性T细胞免疫功能实现的。3.UC病变大鼠结肠粘膜中STAT6蛋白的表达水平明显增高,肠愈宁治疗后可降低血清中STAT6蛋白的表达水平,可能因而干预辅助型Th2细胞体液免疫功能。4.中剂量肠愈宁对于UC疗效优于过低或过高剂量。
Objective:To observe the effects of chang yuning to the expressions of S100、CD83、Foxp3and STAT6, in attempt to study the possible functions of chang yuning、the action mechanisms and the regulations of immune system through them in ulcerative colitis mice.
Method:120Wistar adult rats were divided into normal control group, model blank group, low dose group, high dose group, middle dose group and SASP group regularly, each group had20rats. Except the normal group,100rats were making UC models by composite method according to the syndromes of accumulation of damp-heat., hair removal of back by sodium sulfide, acetone(100ml) and DNCB2.0coated the skins everyday, till the fifteenth days, injected50%DNCB and acetic acid the same place in the sixteen day. Converted dosages by calculate formula between rats and persons' body surface. By garage, the blank and model groups were given distilled water,0.5g/ml、1g/ml、4g/ml Chang Yuning concentration were given10ml/kg per day in low dose group, middle dose group and high dose group. SASP was given0.5g/kg.d. After4weeks, to observe the pathological changes in rat gastric mucosa, expressions of S100、CD83、Foxp3and STAT6.
Result:1.The expressions of S100and CD83were lower in blank group compared with model group, the expressions of western medicine group,low dose group, middle dose group and high dose group were lower compared with the model group but higher than blank group; western medicine group and middle dose group were lower than both low and high dose groups, the level of middle dose group was lower compared with western medicine group.2.About the expression of Foxp3, model group was lower compared with blank group(P<0.01), western medicine group,low dose group, middle dose group and high dose group were higher compared with the model group but lower than blank group (P<0.05), western medicine group and middle dose group were higher than both low and high dose groups (P<0.05), the level of middle dose group grow higher compared with western medicine group(P<0.05).3.About STAT6, the level was lower in blank group compared with model group (P<0.01), the expressions of western medicine group,low dose group, middle dose group and high dose group were lower compared with the model group but higher than blank group(P<0.05), western medicine group and middle dose group were lower than both low and high dose groups, the level of middle dose group was lower compared with western medicine group, but only this difference was not statistically significant (P>0.05).
Conclusion:1.The levels of S100and CD83grew up significantly in UC mice, Chang yu ning can regulate the expressions of them, then reduced the extro-expression of DCs cells.2. The expression of Foxp3was lower in UC rats but Chang yu ning gave it a higher expression, the function of middle dose of Chang Yu Ning is better than SASP obviously, that effect might be through strengthening the immune function of regulatory T cells to achieve.3. STAT6's level in colonic mucosa increased but after the cure of Chang yu ning, it reduced, that may because of the intervention of Th2helper cells of humoral immune function4. Middle dose of Chang Yu Ning for the UC curative effect is better than that of low or high dose.
引文
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