复方角菜酸酯对直肠黏膜急性损伤的治疗作用及其机制研究

目的研究复方角菜酸酯对大鼠直肠黏膜急性损伤的治疗作用及其机制。方法以3%乙酸制作240只SD大鼠直肠损伤模型,分为对照组和实验组。实验组每只经肛门置入复方角菜酸酯栓20mg,2/d,对照组不用药;之后,每组分别在30min和24、72、120h各处死30只大鼠。观察直肠黏膜损伤和病理变化情况,并通过免疫组织化学方法观察该药对CD34、血管内皮生长因子(VEGF)、诱导型一氧化氮合酶(iNOS)、白介素8(IL-8)、金属基质蛋白酶9(MMP9)、缺氧诱导因子(HIF-1α)和增殖细胞核抗原(PCNA)表达的影响。结果用药后24、72、120h,实验组大鼠直肠黏膜损伤计分和充血、水肿、腺体破坏、炎症细胞浸润病理现象明显较对照组轻,修复速度较对照组快,且没有明显的瘢痕形成。损伤后24h,实验组MMP9、VEGF的表达显著降低,损伤后72、120h,6种蛋白的表达均显著低于对照组。实验组的新生血管形成明显低于对照组。结论复方角菜酸酯栓可明显减轻3%乙酸造成的直肠黏膜损伤,促进损伤愈合,且能减轻瘢痕形成;其降低MMP9、VEGF、IL-8、PCNA、iNOS、HIF-1α基因的表达,是直肠黏膜保护机制之一。

Treatment and mechanism of compound carraghenates suppository to rat acute rectal mucous injury

OBJECTIVE: To investigate the treatment and mechanism of compound carraghenates suppository to rat acute rectal mucous injury. METHODS: The model of rat acute rectal mucous injury was established by 3% acetic acid. Two hundred and forty rats were divided equally into control and experimental group. The rats of experimental group were administrated with 20 mg carraghenates suppository via rectum twice a day, but rats of control group were not administrated with carraghenates suppository. Thirty rats in both groups were executed at different time points. The pathologic changes were observed and the rectal mucous injury was scored. Immunohistochemical staining was used to evaluate the effect of carraghenates suppository on expression of VEGF, iNOS, IL-8, MMP9, HIF-1alpha and PCNA in the two groups. RESULTS: The scores of rectal mucous injury was lower, the pathologic changes such as hyperaemia, edema, destroy of glands were less severe, and tissue repair time was shorter in experimental group compared with those in the control group at 24 h, 78 h and 120 h after administration of carraghenates suppository. No obvious cicatrisation was observed in experimental group. Expression ofVEGF and MMP9 was significantly lower in experimental group compared with those in the control group at 24 h after administration. Expression of VEGF, iNOS, IL-8, MMP9, HIF-1alpha and PCNA were statistically decreased in experimental group than those in the control group at 72 h, 120 h after administration. MVD in experimental group was statistically decreased than that in the control group. CONCLUSION: The compound carraghenates suppository can reduce the rectal mucous injury from 3% acetic acid, and accelerate the wound healing without obvious cicatrisation. The compound carraghenates suppository can reduce the expression of MMP9, VEGF, IL-8, PCNA, iNOS and HIF-1alpha, which may play a role in its protective mechanism.