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戴春山,徐王磊,王雄华,沈 刚,沈 潜,陈 彬.川芎嗪对大鼠肠粘连组织MMP-9、TIMP-1和细胞因子表达的影响[J].浙江中西医结合杂志,2013,23(9):695-699
川芎嗪对大鼠肠粘连组织MMP-9、TIMP-1和细胞因子表达的影响
Effects of Ligustrazine on Expressions of Matrix Metalloproteinase-9, Tissue Inhibitor of Metalloproteinase-1 andCytokines in Rats with Intestinal Adhesion Tissues
投稿时间:2013-03-25  
DOI:
中文关键词:  大鼠 肠粘连 川芎嗪 MMP-9 TIMP-1 IL-1β TNF-α TGF-β1
英文关键词:rats intestinal adhesion ligustrazine matrix metalloproteinase-9(MMP-9) tissue inhibitor of metalloproteinase-1(TIMP-1) IL-1 TNF-α TGF-β
基金项目:基金项目:浙江省宁波市医学科技计划项目(No.2010A12)
作者单位
戴春山 浙江省宁波市中医院外一科 
徐王磊 浙江省宁波市中医院外一科 
王雄华 浙江省宁波市中医院外一科 
沈 刚 浙江省宁波市中医院外一科 
沈 潜 浙江省宁波市中医院外一科 
陈 彬 浙江省宁波市中医院外一科 
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中文摘要:
      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(净含川芎嗪约 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。
英文摘要:
      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 interleukin1(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 to4 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 0.1g ligustrazine),while in the rest groups equivalent physiological saline was injected. In the four groups,6 rats were respectively sacrificed on day2,7,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-αandTGF-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 day2 after modeling,but the TIMP-1 ex- pression did not increase to a significantly different level until day7(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. Conclusions: Ligustrazine can inhibit intestinal adhesion in rats by reducing IL-1,TNF-α,and TGF-β and regulatingMMP-9 and TIMP-1 in the intestinal tissues
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