大承气汤对脓毒症大鼠髓系细胞触发受体-1表达的影响

摘要

Objective To study the effect of Dachengqi decoction on expression of triggering receptor on myeloid cell 1(TREM-1)in septic rats in order to further provide a theoretical basis concerning the mechanism of this decoction for treatment of sepsis. Methods 100 male Sprague-Dawley(SD)rats were randomly divided into five groups:normal control,sham operation,sepsis model,low-dose and high-dose Dachengqi decoction groups (each,n=20). The sepsis models were reproduced by cecal ligated perforation(CLP). The low-dose and high-dose Dachengqi decoction groups were lavaged separately by low dose(5 mL/kg)and normal dose(10 mL/kg)Dachengqi decoction at 2 hours before CLP and after CLP twice per day(interval 8 hours),and the other three groups were lavaged with 10 mL/kg normal saline. Five rats in each group were killed randomly at the time points of 6,12,24,48 hours after CLP;the abdominal aorta blood and the liver tissue were collected. The plasma levels of TREM-1,interleukin-6 (IL-6),tumor necrosis factor-α(TNF-α)were tested by enzyme linked immunosorbent assay(ELISA). The expression level of TREM-1 mRNA in the liver was measured by reverse transcription - polymerase chain reaction (RT-PCR). Results Compared with normal control group and sham operation group, the plasma levels of TREM-1, IL-6, TNF-α and the expression of liver TREM-1 mRNA were increased significantly in model group. Compared with model group,the above indexes in low-dose and high-dose Dachengqi decoction groups were reduced obviously,the changes being more marked in the high-dose group;the levels of TREM-1,IL-6 at 6 hours after operation and the levels of TNF-αand TREM-1 mRNA at 24 hours after operation in high-dose group were lower than those of low-dose group〔6 hours TREM-1(ng/L):179.19±4.43 vs. 213.86±2.84,6 hours IL-6 (ng/L):136.80±7.70 vs. 162.90±3.87;24 hours TNF-α(ng/L):71.61±5.07 vs. 108.53±6.29,24 hours TREM-1 mRNA:24.33±3.16 vs. 27.22±3.34,all P<0.05〕. Conclusion The partial mechanism of the efficacy of Dachengqi decoction for treatment of sepsis was probably related to the inhibition of TREM-1 expression.%目的：观察大承气汤对脓毒症大鼠髓系细胞触发受体-1（TREM-1）表达的影响，为进一步探讨大承气汤治疗脓毒症的作用机制提供理论依据。方法将100只雄性SD大鼠按随机数字表法分为正常对照组、假手术组、模型组以及大承气汤低剂量和高剂量组，每组20只。采用盲肠结扎穿孔术（CLP）制备脓毒症模型，大承气汤低剂量和高剂量组于术前2 h和术后（每日两次，相隔8 h）分别灌胃大承气汤5 mL/kg、10 mL/kg，其余3组以生理盐水10 mL/kg灌胃。各组于制模后6、12、24、48 h分别随机处死5只大鼠，经腹主动脉采血并取肝脏组织，用酶联免疫吸附试验（ELISA）检测各组大鼠血浆TREM-1、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）的含量，逆转录-聚合酶链反应（RT-PCR）检测TREM-1 mRNA的表达。结果与正常对照组和假手术组比较，模型组大鼠血浆TREM-1、IL-6、TNF-α含量及肝组织TREM-1 mRNA表达均升高；大承气汤低剂量和高剂量组上述各检测指标均较模型组下降，且以高剂量组变化更显著，TREM-1及IL-6于术后6 h起、TNF-α及TREM-1 mRNA于术后24 h起两组比较差异有统计学意义〔6 h TREM-1（ng/L）：179.19±4.43比213.86±2.84，6 h IL-6（ng/L）：136.80±7.70比162.90±3.87；24 h TNF-α（ng/L）：71.61±5.07比108.53±6.29，24 h TREM-1 mRNA：24.33±3.16比27.22±3.34，均P＜0.05〕。结论大承气汤治疗脓毒症的部分机制可能与其抑制TREM-1表达有关。