谷氨酰胺和地塞米松对脓毒症幼年大鼠肝脏肿瘤坏死因子-α与基质金属蛋白酶3的影响

Effects of glutamine and dexamethasone on the expression of tumor necrosis factor alpha and matrix metalloproteinase 3 in rat liver with sepsis

目的:通探讨谷氨酰胺(Gln)和地塞米松(Dex)对脓毒症肝损伤的保护作用方法:ip大肠杆菌脂多糖(LPS)制备幼年大鼠脓毒症模型,按照ip药物不同分为对照组(C,n =8,ip生理盐水1 mL/kg);内毒素组(L,n=40,ip LPS 4 mg/kg),治疗组(T,n=40,ip LPS 4 mg/kg后1 h ip Dex 5 mg/kg+Gln 1 mL/kg),在注射内毒素后0 h(只限对照组),2,4,6,24和72 h取肝右叶,采用免疫组化的方法测定肝组织中肿瘤坏死因子(TNF-α)和基质金属蛋白酶3(MMP3)蛋白质合成水平。结果:与C相比,L组TNF-α蛋白质表达明显高于对照组(P<0.01),24 h达高峰,72 h虽然有所降低但仍明显高于对照组(P<0.05).T组各时点TNF-α蛋白质表达均高于对照组,但增高幅度明显低于L组(P<0.01),与对照组相比,L组MMP3蛋白质表达明显升高,24 h达高峰,72 h有所降低,但仍高于对照组(P<0.01);T组较L组明显减低(P<0.01)。L和T组肝脏组织中TNF-α与MMP3改变均呈明显正相关(r= 0.928,r=0.939)。结论:联合应用谷氨酰胺与地塞米松可以抑制TNF-α和MMP3的合成,从而减轻脓毒症幼年大鼠的肝脏损伤和重塑。

AIM： To explore the effect of glutamine （Gln） and dexamethasone （Dex） on the production of tumor necrosis factor alpha （TNF-ct） and matrix metaUoproteinase 3 （MMP3） in the liver of young rats with endotoxemia. METHODS： Endotoxemia models were established by intraperitoneal injection of lipopolysaccharide （LPS） in 88 18-day-old young wistar rats. The rats were then randomly divided into three groups： control group （C, normal saline 1 mL/kg ip, n = 8）, LPS group （L, LPS 4 mg/kg ip, n =40） and treatment group （T, LPS 4 mg/kg ip, followed 1 hour later by Dex 5 mg/kg plus 13.46% Gln 1 mL/kg ip, n = 40）. The rats were sacrificed at 0, 2, 4, 6, 24 and 72 h. Liver was isolated, fixed and cut into slices to examine the protein expression of TNF-α and MMP3 by immunohistochemistry. RESULTS： The protein expression of TNF-α in the L group gradually increased with disease development, until it peaked at 6-24 hours, which was significantly higher than that in the control group （P 〈 0.01）; it then slowly decreased until 72 hours but was still higher than that in the controls （P 〈 0.05）. The variation in the T group was paralleled to that in the L group but significantly milder than that in the L group （P 〈 0.01）. In the L group, the change in MMP3 was similar to that for TNF-α; the peak was at 24 hours, but at 72 hours, it was still higher than in the controis （P 〈 0.01）. In the T group, the production of MMP3 was significantly higher than that in the controls （P 〈 0.01）, but significantly lower than that in the L group （P 〈 0.01）. There were positive correlations between the expression of TNF-α and MMP3 during sepsis （L group, r = 0.928; T group, r= 0.939）. CONCLUSION： Combination of Gln and Dex can prevent the damage and rebuilding of liver with sepsis by decreasing the productions of TNF-α and MMP3.