CAJ | 학술논문

目的：观察川芎嗪对肠粘连模型大鼠粘连肠组织基质金属蛋白酶-9（MMP-9）、基质金属蛋白酶抑制因子-1（TIMP-1）表达及血清白细胞介素-1（IL-1）、肿瘤坏死因子-α（TNF-α）及转化生长因子（TGF-β）水平的影响，探讨川芎嗪预防肠粘连作用机制。方法：72只SD雄性大鼠随机分为正常对照组、假手术组、手术组及川芎嗪组，每组18只。正常对照组不行手术，假手术组仅行腹腔开关术，川芎嗪组术后每天腹腔注射川芎嗪溶液10mL（净含川芎嗪<0.1g），其余三组注射等量生理盐水。各组于术后第2、7、14天取血，肉眼观察肠粘连的程度分级；酶联免疫吸附法测定血清细胞因子IL-1、TNF-α、TGF-β。免疫组织化学染色加图像分析法观测MMP-9及TIMP-1表达。结果：手术组及川芎嗪组肠粘连程度显著增加（P<0.05），与手术组比较，川芎嗪组肠粘连程度明显减轻（P<0.05）。与手术组比较，川芎嗪组IL-1、TNF-α及TGF-β水平均明显降低（P<0.05或P<0.01）。术后2天，与手术组比较，川芎嗪组肠组织MMP-9表达显著降低（P<0.05），TIMP-1未见明显改变（P>0.05）。术后7天及14天，川芎嗪组肠组织TIMP-1表达较手术组有显著增高（P<0.05），MMP-9无明显改变（P>0.05）。结论：川芎嗪可能通过影响血细胞因子IL-1β、TNF-α和TGF-β1水平及肠组织MMP-9和TIMP-1表达，一定程度上抑制大鼠肠粘连。
목적：관찰천궁진대장점련모형대서점련장조직기질금속단백매-9（MMP-9）、기질금속단백매억제인자-1（TIMP-1）표체급혈청백세포개소-1（IL-1）、종류배사인자-α（TNF-α）급전화생장인자（TGF-β）수평적영향，탐토천궁진예방장점련작용궤제。방법：72지SD웅성대서수궤분위정상대조조、가수술조、수술조급천궁진조，매조18지。정상대조조불행수술，가수술조부행복강개관술，천궁진조술후매천복강주사천궁진용액10mL（정함천궁진<0.1g），기여삼조주사등량생리염수。각조우술후제2、7、14천취혈，육안관찰장점련적정도분급；매련면역흡부법측정혈청세포인자IL-1、TNF-α、TGF-β。면역조직화학염색가도상분석법관측MMP-9급TIMP-1표체。결과：수술조급천궁진조장점련정도현저증가（P<0.05），여수술조비교，천궁진조장점련정도명현감경（P<0.05）。여수술조비교，천궁진조IL-1、TNF-α급TGF-β수평균명현강저（P<0.05혹P<0.01）。술후2천，여수술조비교，천궁진조장조직MMP-9표체현저강저（P<0.05），TIMP-1미견명현개변（P>0.05）。술후7천급14천，천궁진조장조직TIMP-1표체교수술조유현저증고（P<0.05），MMP-9무명현개변（P>0.05）。결론：천궁진가능통과영향혈세포인자IL-1β、TNF-α화TGF-β1수평급장조직MMP-9화TIMP-1표체，일정정도상억제대서장점련。
Objective:To determine the expressions of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1(TIMP-1) in the tissues of intestinal adhesion and cytokine interleukin 1(IL-1),tumor necrosis factor alpha(TNF-α) and transformation growth factor(TGF-β) in blood sera of rats, in order to explain the mech-anism of ligustrazine on intestinal adhesion. Methods:Seventy-two SD male rats were randomly assigned to 4 groups:normal group,sham operation group,operation group,and drug group,18 rats in each group. Traumatic model of intestinal adhesion model was established in the operation and drug group. In the sham operation group,the anesthesia and laparotomy were the same as the operation group, but no intestinal tissue was injured and no mesenteric artery was clamped. In the drug group,rats were intraperitonealiy injected with 10 mL of ligustrazine solution (about 0.1 g ligustrazine),while in the rest groups equivalent physiological saline was injected. In the four groups,6 rats were respectively sacrificed on day 2,7,and 14 after modeling, and tissues of serous membrane in adhesive area were taken. Under macroscopic observation,intestinal adhesion were classified. Elisa method was used for determination of cell factor IL-1,TNF-α,and TGF -β. The expressions of MMP-9 and TIMP-1 in the intestinal adhesive tissues and the normal intestinal tissues were determined by immunohistochemistry assay and image analy-sis. Results:(1)Compared with the sham operation and normal groups,the intestinal adhesion degree in the opera-tion and drug group significantly increased (P<0.05);and compared with the operation group,the drug group had lower degree of interstinal adhesion(P<0.05). (2)Compared with the operation group,the levels of IL-1,TNF-αand TGF -β in the drug group significantly decreased,with statistically significant difference (P<0.05 or P<0.01). (3) Compared with the operation group,the MMP-9 expression reduced on day 2 after modeling,but the TIMP-1 ex-pression did not increase to a significantly different level until day 7 (all P<0.01). On day 7 and 14,the drug group had the expressions of TIMP-1 increased (P<0.05),but did not have a significant increase in MMP-9. Con-clusions:Ligustrazine can inhibit intestinal adhesion in rats by reducing IL-1,TNF-α,and TGF-β and regulating MMP-9 and TIMP-1 in the intestinal tissues.