五味苦参肠溶胶囊对溃疡性结肠炎小鼠半胱天冬氨酸蛋白酶1、白细胞介素-1β蛋白的影响

Effects of composite sophora colon-soluble capsules on level of caspase-1, IL-1β in mice with ulcerative colitis

目的观察新药五味苦参肠溶胶囊(composite sophora colon-soluble capsules,CSCC)对葡聚糖硫酸钠(dextran sulfate sodium salt,DSS)诱导的溃疡性结肠炎(ulcerative colitis,UC)小鼠结肠组织中半胱天冬氨酸蛋白酶-1(Caspase-1)、白介素-1β(interleukin 1-beta,IL-1β)蛋白含量的影响。方法 BALB/C小鼠50只,随机分成模型组、空白对照组、五味苦参低剂量组[1.92 g/(kg·d)]、五味苦参中剂量组[3.84 g/(kg·d)]、五味苦参高剂量组[7.68 g/(kg·d)],每组10只。除空白组外,其余各组自由饮用3%葡聚糖硫酸钠溶液7 d,之后空白对照组与模型组采用0.9%氯化钠注射液灌肠7 d,中药组分别按高、中、低剂量进行CSCC灌肠7 d。各组取结肠组织观察病变程度,测量其结肠长度、结肠系数、脾系数,并行苏木精-伊红染色法染色、光镜下观察结肠组织病理变化,ELISA法检测小鼠结肠组织中Caspase-1、IL-1β的蛋白含量。结果结肠组织HE染色:与空白组相比,模型组结肠组织结构紊乱,杯状细胞减少,炎症细胞浸润,腺体破坏或消失、局部有水肿,而五味苦参各组炎症较轻。ELISA法检测:与模型组相比,五味苦参各组小鼠结肠组织中Caspase-1[(模型组vs中剂量组,(27.02±4.23)ng/L vs(22.73±1.68)ng/L,P<0.05]、IL-1β蛋白含量均有所降低[模型组vs中剂量组,(87.79±11.34)ng/L vs(75.49±8.41)ng/L,P<0.05]。结论五味苦参肠溶胶囊可降低DSS诱导的UC小鼠结肠组织中Caspase-1、IL-1β蛋白含量,减轻结肠组织的病理损伤。

Objective To observe the effect of composite sophora colon-soluble capsules （CSCC） on expressions of caspase-1 and interleukin 1-beta （IL-1β ） in colon tissues of mice with ulcerative colitis （UC） induced by dextran-sulfate-sodium （DSS）. Methods Fifty BALB/C mice were randomly divided into five groups： normal control group （Nctrl group）, model control group （Model group）, low dose of CSCC group [1.92 g/（kg · d）], moderate dose of CSCC group [3.84 g/（kg · d）], and high dose of CSCC group [7.68 g/（kg · d）], with ten mice in each group. After drinking water with 3% DSS for seven days in all groups except Nctrl, Nctrl group and model group received 0.9% saline enema for seven days, while CSCC groups received CSCC suspension enemas at different concentration respectively as mentioned before. The pathology of colon tissues were observed, and the length of colon, the coefficient of colon and spleen were measured. Then the pathological changes of colon tissues were stained by HE staining and observed under microscope, and the protein levels of Caspase-1 and IL-1β in colon tissues were detected by ELISA. Results Compared with Nctrl group, disordered colon tissue structure, decrease of goblet cell, infiltrated inflammatory cells and destructed or disappeared gland were observed in model group by HE staining, while the inflammation reduced to different degree in CSCC groups. Compared with the model group, CSCC groups expressed significantly higher level of Caspase-1 [model group vs moderate dose CSCC group： （27.02 ± 4.23） ng/L vs （22.73 ± 1.68） ng/L, P 〈 0.05] and IL-1β ]model group vs moderate dose CSCC group： （87.79 ± 11.34） ng/L vs （75.49 ± 8.41） rig/L, P 〈 0.05]. Conclusion CSCC can reduce the expressions of Caspase-1 and IL-1β in mice with DSS-induced UC, and alleviate the pathological injury of gut.