大黄甘草汤对急性坏死性胰腺炎大鼠并发的肺损伤的影响

目的 观察大黄甘草汤对急性坏死性胰腺炎(ANP)大鼠并发肺损伤的治疗效果,探讨其作用机制.方法 90只Wistar大鼠按完全随机法分为假手术组、ANP组和大黄甘草汤治疗(治疗)组,每组30只.采用逆行胰胆管注射4%牛磺胆酸钠方法制备ANP模型.治疗组在制模后给予大黄甘草汤(0.25 g/ml)0.6 ml/100 g体重灌胃,1次/12 h;假手术组与ANP组予等量生理盐水灌胃.术后6、12、24 h分批处死大鼠,取胰腺及肺组织行病理学检查并评分;测血清及肺组织IL-6、IL-10、TNF-α水平;免疫组化法检测肺组织Toll样受体4(TLR4)的表达量.结果 制模后12 h,假手术组、ANP组和治疗组的血IL-6水平分别为(14.4±4.0)pg/ml、(171.4±41.3)pg/ml、(156.9±34.7)pg/ml,IL-10水平为(13.7±4.5)pg/ml、(120.5±23.7)pg/ml、(148.3±44.4)pg/ml,TNF-α水平为(22.4±4.7)pg/ml、(261.3±51.4)pg/ml、(235.3±45.9)pg/ml;肺组织IL-6水平为(257.3±55.9)pg/g、(2578.3±403.0)pg/g、(2370.0±491.0)pg/g,IL-10水平为(80.8±20.8)Pg/g、(642.0±107.3)pg/g、(695.3±151.7)Pg/g,TNF-α水平为(207.6±98.6)pg/g、(1769.1±635.6)Pg/g、(1401.1±450.5)pg/g;胰腺病理评分为0、7.0±1.3、6.3±1.0;肺脏病理评分为0、6.3±1.4、5.6±1.0;肺组织TLR4表达量为0.09 ±0.03、0.59±0.09、0.52±0.08.ANP组和治疗组的上述指标均显著高于假手术组(P值均＜0.01);除IL-10外,治疗组的指标又显著低于ANP组(P值均＜0.05).肺组织病理学损伤与胰腺组织损伤呈正相关(r=0.807,P＜0.01),与TLR4表达水平亦呈正相关(r=0.519,P＜0.01).结论 大黄甘草汤可快速改善ANP并发的肺损伤,其机制可能与抑制TLR4的表达、降低IL-6和TNF-α、升高IL-10水平有关.

Effect of Dahuang Gancao decoction on lung injury complicated by acute necrotizing pancreatitis

Objective To investigate the treatment effects of dahuang gancao decoction on lung Injury complicated by acute necrotizing pancreatitis and explore its mechanism. Methods 90 Wistar rats were randomly divided into 3 groups, namely sham-operated group (SO), ANP group (ANP), dahuang gancao decoction treatment group (DG). 4% sodium taurocholate was injected into the pancreatic duct to induce ANP. Dahuang gancao decoction(0.25 g/ml) 0.6 ml/100 g weight was gavaged in the DG group, the same volume of normal saline was gavaged in the SO and ANP group, which was repeated 12 h later. After 6 h, 12 h, 24 h, all rats were sacrificed, pancreas and lung tissues were harvested to observe the pathological changes and the pathological changes were scored. IL-6, IL-10, TNF-α levels of serum and lung tissue were measured,and the changes of toll-like receptor 4 (TLR4) expression in lung tissue was determined by immunohistochemical method. Results 12 h after ANP induction, the serum levels of IL-6 in SO, ANP, DG group were (14.4±4.0)pg/ml, (171.4 ±41.3)pg/ml, (156.9 ±34.7)pg/ml; the serum levels of IL-10 were (13.7 ±4.5)pg/ml, (120.5 ±23.7)pg/ml, (148.3 ±44.4)pg/ml; the serum levels of TNF-α were (22.4 ±4.7)pg/ml, (261.3 ±51.4)pg/ml, (235.3 ±45.9)pg/ml; the lung tissue levels of IL-6 were (257.3 ±55.9)pg/ml,(2578.3 ±403.0)pg/ml,(2370.0 ±491.0)pg/ml; the lung tissue levels of IL-10 were (80.8 ±20. 8)pg/g, (642.0 ± 107.3)pg/g, (695.3 ± 151.7) pg/g, the lung tissue levels of TNF-α were (207.6 ±98.6)pg/g, (1769.1 ±635.6) pg/g, (1401.1 ±450.5) pg/g; the pancreas pathological scores were 0, 7.00 ±1.33, 6.30 ± 0.95; the lung pathological scores were 0, 6.30 ± 1.42, 5.60 ± 0.97; the expressions of TLR4in lung tissue were 0.09 ± 0. 03, 0.59 ± 0. 09, 0. 52 ± 0. 08. The values in the ANP and DG groups were significantly higher than those in SO group (P < 0. 01 ); except for IL-10, all values in the DG groups were significantly lower than those in ANP group (P < 0.05); there was a positive association between lung and pancreas scores (r =0.807, P<0.01), and lung score was positively associated with the expression of TLR4(r = 0.519, P < 0.01 ). Conclusions Dahuang ganeao decoction may quickly improve lung injury complivated by ANP. The mechanism may involve inhibiting the expression of TLR4 and down-regulating the expression of IL-6, TNF-α, up-regulating the. Expression of IL-10.