复方纳米银抗菌水凝胶对溃疡性结肠炎大鼠肠道屏障功能的影响

Effects of Compound Nano- silver Antimicrobial Hydrogel on Intestinal Barrier Function of Rats with Ulcerative Colitis

目的探讨应用复方纳米银抗菌水凝胶灌肠治疗溃疡性结肠炎(UC)大鼠对其肠道屏障功能的影响、机制以及治疗效果。方法选取健康成年雄性清洁级Wistar大鼠50只随机(随机数字表法)分为空白对照组、UC模型组、纳米银组、复方纳米银组(含地塞米松)、对氨基水杨酸组各10只。空白对照组正常饲养,其余组采用2、4二硝基氯苯及乙酸复合法进行UC造模,造模成功后,分别以相应药物保留灌肠7天。灌肠治疗7天后抽取血标本检测各组大鼠血浆D-乳酸(D-Lac_)及血清炎症指标IFN-γ、IL-10、TGF-β1。随后处死大鼠,取大鼠结肠组织,HE染色后进行病理检查,计算肠粘膜损伤的HPS评分并检测UC大鼠肠粘膜咬合蛋白(occludin)的表达水平。结果与空白对照组相比,UC模型组大鼠血清IFN-γ、TGF-β1水平、血浆D-Lac水平明显升高,IL-10及肠粘膜occludin表达水平降低(P<0.05)。治疗7天后,复方纳米银组大鼠血浆D-Lac、血清IFN-γ、TGF-β1水平较UC模型组及其他治疗组降低,血清IL-10及肠粘膜occludin蛋白表达水平升高,并且肠粘膜损伤的病理HPS评分明显低于UC模型组和其他各治疗组(均P<0.01)。结论应用复方纳米银抗菌水凝胶灌肠治疗可显著减轻UC大鼠肠道的炎症反应,改善肠道屏障功能障碍,减轻肠粘膜的损伤。

Objective To study the effects of compound nano - silver antibacterial hydrogel on the intestinal barrier function of rats with ulcerative colitis （UC）. Methods Fifty healthy adult male Wistar rats of clean grade were randomly di- vided into control group, UC model group, nano - silver group, compound nano - silver group （ including dexamethasone） and P -aminosalieylic acid group, 10 rats in each group The rats in the control group were normally fed. UC modeling were made in other groups by 2, 4 - dichlorobenzene and acetic acid compound method. After successful modeling, corresponding drug retention enema for 7 days was treated in those groups, respectively. Blood samples were collected in each group after 7 days treatment and plasma D -lactic acid （D -Lac） and serum inflammatory markers IFN -γ, IL- 10, TGF-β1 were de- tected. Then the rats were sacrificed and colon tissues and HE chromosome of rats were drawn to calculate intestinal mucosal injury and HPS ratings rat intestinal occlusion UC proteins （occludin） expression levels after pathological examination. Re- sults Compared with the control group, levels of serum IFN - γ, TGF - β1 and plasma D - Lac in UC modeling groups sig- nificantly increased, IL - 10 level and occludin expression level on the intestinal mucosa significantly reduced （P 〈 0. 05 ）. After 7 days treatment, levels of serum IFN-γ, TGF- β1 and plasma D- Lac in nano- silver antibacterial hydrogel group were lower than those in UC modeling and other treatment groups and IL - 10 level and occludin expression level increased and HPS pathological mucosal injury scores were significantly lower than that in UC modeling group and other treatment groups （ all P 〈 0. 01 ）. Conclusion Compound Nano - silver antimicrobial hydrogel enema treatment can significantly reduce the inflammatory reactions of UC rats, and improve intestinal barrier dysfunction and reduce damage on intestinal mucosa.