论文部分内容阅读
目的评价口服耐受和经鼻耐受治疗对大鼠实验性结肠炎的疗效,以及分别加用佐剂对其疗效的影响。方法建立三硝基苯磺酸(TNBS)实验性结肠炎大鼠模型。以卵白蛋白(OVA)为诱导抗原,脂多糖为佐剂。将已建立的 TNBS 结肠炎大鼠模型根据不同的干预方法分为结肠炎组、口服耐受组、经鼻耐受组、口服加佐剂组、经鼻加佐剂组、佐剂对照组和空白对照组。各组大鼠经上述不同治疗后均于灌肠第21天处死,以肠道大体和组织病理学评分为标准评价治疗效果,以脾淋巴细胞增殖实验评价黏膜耐受诱导效果。结果肠道大体评分(平均秩次9.5 vs 3.5,P<0.01)和组织病理学评分(平均秩次9.5 vs 3.5,P<0.01)显示 TNBS 诱导的实验性结肠炎模型在无干预情况下可持续至第21天仍有肠道炎症。脾淋巴细胞增殖实验结果显示,在大鼠结肠炎状态下,口服耐受组不能诱导机体对 OVA 的免疫耐受,而口服加佐剂组(0.11±0.05 vs 0.30±0.13,P<0.05)、经鼻耐受组(0.12±0.07,P<0.05)和经鼻加佐剂组(0.06±0.04 vs 0.30±0.13,P<0.05)均可诱导机体免疫耐受,不同途径诱导的免疫耐受效果差异无统计学意义。与结肠炎组大鼠相比,口服加佐剂组(大体评分3.0±1.3 vs 6.3±0.8,组织学病理评分3.0±1.1 vs 7.5±1.0,均 P<0.05),经鼻加佐剂组(大体评分2.0±0.6,组织学病理评分2.7±1.0,均 P<0.05)和佐剂对照组(大体评分4.3±1.0,组织学病理评分4.6±1.6,均 P<0.05)大鼠的肠道评分均显著较低。其中经鼻加佐剂组大鼠的肠道评分下降最显著。结论 TNBS 实验性结肠炎干扰了口服耐受的诱导,但不影响经鼻耐受的诱导。加用佐剂的口服耐受和加用佐剂的经鼻耐受对实验性结肠炎均有一定治疗作用,单独应用佐剂也有一定疗效,其中加用佐剂的经鼻耐受疗效最好。
Objective To evaluate the effects of oral tolerance and nasal tolerance treatment on experimental colitis in rats and the effects of adjuvant and adjuvant on their therapeutic effects. Methods The rat model of trinitrobenzene sulfonic acid (TNBS) experimental colitis was established. Ovalbumin (OVA) as antigen, lipopolysaccharide adjuvant. The established TNBS-induced colitis rat model was divided into colitis group, oral tolerance group, nasal tolerance group, oral plus adjuvant group, nasal plus adjuvant group, adjuvant control group and blank control group according to different intervention methods group. The rats in each group were sacrificed on the 21st day after the above treatments, and the therapeutic effects were evaluated according to the general and histopathological score of gut. The mucosal tolerance induced by splenic lymphocyte proliferation was evaluated. Results Overall gut scores (mean rank 9.5 vs 3.5, P <0.01) and histopathological scores (mean rank 9.5 vs 3.5, P <0.01) showed that the TNBS-induced experimental colitis model was sustainable without intervention Intestinal inflammation remained on day 21. The experimental results of splenic lymphocyte proliferation showed that oral tolerance group could not induce the immune tolerance to OVA in the condition of colitis in rats, while the oral administration plus adjuvant group (0.11 ± 0.05 vs 0.30 ± 0.13, P <0.05) The immune tolerance of the mice in nasal tolerance group (0.12 ± 0.07, P <0.05) and nasal plus adjuvant group (0.06 ± 0.04 vs 0.30 ± 0.13, P <0.05) all induced immune tolerance differences Statistical significance. Compared with the rats in the colitis group, the rats in the adjuvant plus adjuvant group (general score 3.0 ± 1.3 vs 6.3 ± 0.8, histopathological score 3.0 ± 1.1 vs 7.5 ± 1.0, all P <0.05) 2.0 ± 0.6, histological grade 2.7 ± 1.0, both P <0.05) and adjuvant control group (general score 4.3 ± 1.0, histological score 4.6 ± 1.6, both P <0.05) low. The nasal plus adjuvant group, the most significant decline in intestinal scores. Conclusions TNBS experimental colitis disrupts oral tolerance induction but does not affect nasal tolerance induction. Adjuvant oral adjuvant and adjuvant nasal tolerance have a certain therapeutic effect on experimental colitis, adjuvant alone has some curative effect, of which adjuvant nasal tolerance is the best .