高通量测序探讨胰腺炎加重肝损伤的研究

Through high - throughput sequencing technologies to explore the mechanism of pancreatitis aggravating liver damage

目的探讨急性胰腺炎（AP）加重肝脏损伤的机制。方法将sD大鼠随机分为AP组和对照组（NC），采用牛磺胆酸钠逆行胰胆管注射的方法建立AP模型，造模后6h经下腔静脉采血，检测血清淀粉酶、脂肪酶水平、胰腺水含量，同时收集肝脏组织，用于提取RNA。通过转录组测序（RNA—seq）的方法分析AP加重肝损害的相关基因和通路改变。结果AP组与NC组比，其血清淀粉酶[（8964．65±401．23）U／L]和脂肪酶[（2350．00±201．90）U／L]含量明显上升（P〈0．05）；胰腺水含量AP组[（79．42±1．21）％]显著高于NC组[（70．14±1．02）％]；RNA—seq结果显示两组间共有2249个差异表达基因，其中564个表达上调，1685个表达下调。京都基因与基因组百科全书（KEGG）通路富集结果由高到低为代谢通路、炎性因子通路、趋化因子通路、Toll样受体通路等。结论AP可能通过炎性因子、Toll样受体（TLR）等通路介导了对肝脏的损伤。

Objective To explore the mechanism of acute pancrea titis （AP） aggravating liver damage. Methods SD rats were randomly divided into negative control （NC） and AP group. We use the method of sodium taurocholate retrograde pancreatic duct injection to establish the model of AP. After 6 h of anesthesia, the blood were collected from the inferior vena cava to detect the levels of serum amylase and lipase. The liver tissue was collected immediately in order to extract total RNA. The genes and related pathways were analyzed by RNA - seq. Results Compared to NC group, the levels of serum amylase [ （8 964.65 ±.401.23） U/L] and lipase [ （2 350.00 ±201.90） U/L] were significantly higher in AP group （ P 〈 0. 05 ） ; the pancreatic water content in AP group [ （ 79.42 ±. 1.21 ） % ] were significantly higher than NC group [ （70. 14 ± 1.02）% ] ; RNA - seq results showed that there were 2249 differently ex- pressed genes between AP and NC group, among which 564 genes were up - regulated and 1685 genes were down -regulated. Kyoto gene and genome encyclopedia （KEGG） analysis results from high scores to low scores were： metabolic pathway.cytokine pathway.chemokine signaling pathway.Toll -like receptor signa- ling pathway. Conclusion Cytokine pathway, Toll -like receptor signaling pathway may be involved in the mechanism of AP aggravating liver damage.