吡格列酮抑制肺组织TLR2、TLR4的mRNA表达进而减轻重症急性胰腺炎肺损伤的机制探索

目的:探讨吡格列酮减轻重症急性胰腺炎肺损伤的机制。方法:将30只健康雄性SD大鼠，随机（随机数字法）分为假手术组、模型组、吡格列酮组，每组10只。假手术组大鼠麻醉后，胰胆管逆行注射生理盐水。模型组麻醉后，胰胆管逆行注射牛磺胆酸钠构建重症急性胰腺炎肺损伤模型。吡格列酮组腹腔注射吡格列酮后再构建模型。每组随机选择6只大鼠于手术后12 h剖杀，留取肺组织及静脉血。检测并比较三组大鼠血清淀粉酶水平及肺组织匀浆中TNF-α、NO水平；采用RT-PCR检测并比较三组肺组织TLR2 mRNA、TLR4 mRNA表达情况；比较三组间肺组织病理损伤评分和肺渗漏指数。分析TLR2和TLR4的mRNA表达情况与肺病理损伤评分、肺渗漏指数的相关性。结果:模型组血清淀粉酶及肺组织匀浆中TNF-α、NO水平均显著高于假手术组，吡格列酮组上述指标水平均显著低于模型组，差异均有统计学意义（ P<0.05）。模型组肺组织TLR2 mRNA、TLR4 mRNA表达水平以及肺组织病理损伤评分、肺渗漏指数均显著高于假手术组，吡格列酮组上述指标均显著低于模型组，差异均有统计学意义（ P<0.05）。由Spearman相关分析可见肺组织TLR2 mRNA、TLR4 mRNA表达水平与肺组织病理损伤评分呈显著正相关关系（rs=0.959， P<0.001；rs=0.924， P<0.001）；由Pearson相关分析可见肺组织TLR2 mRNA、TLR4 mRNA表达水平与肺渗漏指数均呈显著正相关关系（r=0.957， P<0.001；r=0.958， P<0.001）。 结论:吡格列酮可能通过抑制肺组织TLR2 mRNA、TLR4 mRNA的表达进而减轻重症急性胰腺炎肺损伤程度。

Exploration on the mechanism of pioglitazone in alleviating severe acute pancreatitis induced lung injury by inhibiting the expression of TLR2 and TLR4's mRNA in lung tissue

Objective:To explore the mechanism of pioglitazone in reducing lung injury induced by acute pancreatitis.Methods:Thirty healthy male SD rats were randomly(random number) divided into the sham operation group, model group and pioglitazone group, with 10 rats in each group. After anesthesia, the rats in the sham operation group were injected with normal saline retrogradely through the pancreaticobiliary duct. In the model group, after anesthesia, the rats were retrogradely injected with sodium taurocholate into the pancreaticobiliary duct to construct the lung injury model of severe acute pancreatitis. In the pioglitazone group, the model was established after intraperitoneal injection of pioglitazone. Six rats in each group were randomly selected and killed 12 h after operation, and then lung tissue and venous blood were collected. The levels of serum amylase and TNF-α and NO in lung tissue homogenate were detected and compared among the three groups; the expression of TLR2 mRNA and TLR4 mRNA in lung tissue was detected by RT-PCR and compared among the three groups; the lung tissue pathological injury score and lung leakage index were calculated and compared among the three groups. The correlation of TLR2 and TLR4’s mRNA expression with lung tissue pathological injury score and lung leakage index was analyzed.Results:The levels of serum amylase and the levels of TNF-α and NO in lung tissue homogenate in the model group were significantly higher than those in the sham operation group, and the above indexes in the pioglitazone group were significantly lower than those in the model group ( P<0.05). The expression levels of TLR2 mRNA and TLR4 mRNA in lung tissue, the lung tissue pathological injury score and lung leakage index in the model group were significantly higher than those in the sham operation group, and the above indexes in the pioglitazone group were significantly lower than those in the model group ( P<0.05). Spearman correlation analysis showed that the expression levels of TLR2 mRNA and TLR4 mRNA in lung tissue were significantly positively correlated with the lung tissue pathological injury score ( rs=0.959, P<0.001; rs=0.924, P<0.001). Pearson correlation analysis showed that the expression levels of TLR2 mRNA and TLR4 mRNA in lung tissue were significantly positively correlated with the lung leakage index ( r=0.957, P<0.001; r=0.958, P<0.001). Conclusions:Pioglitazone may reduce the severity of severe acute pancreatitis induced lung injury by inhibiting the expression of TLR2 mRNA and TLR4 mRNA in lung tissue.