| Objective: The liver is one of the the major target organs being attactedduring severe acute pancreatitis (Severe Acute Pancreatitis, SAP), and hepaticinjury will further deteriorate the body functions as a whole.83%of the deathtoll of SAP were found concurrent with hepatic injury. However, itspathogenesis is not yet completely clear and lack of effective treatment.Currently, the role of thoracic duct/mesenteric lymph in septic shock, severeburns or severe trauma has been recognized. Researchers believe that lymphacts as an important pathway for the transmission of cytokines, endotoxin,bacteria, etc. The polyphenol acid extracted from the traditional Chineseherbal medicine—Salvia miltiorrhiza,has been applied in the clinicaltreatment for many cardiovascular and cerebrovascular diseases,with itsstrong efficacy of regulation of platelet function, enhancement of the body’santioxidant capacity, improvement of microcirculation and cellular energymetabolism. Therefore, the aim of this study is to investigate thepathogenesis of SAP-associated liver injury in rats, to explore the therapeuticvalue of polyphenol acid of Salvia miltiorrhiza and thoracic duct lymph onSAP-associated liver damage, and to provide an experimental basis forclinical application.Method: The144healthy male SD (Sprague-Dawley) rats are groupedaccording to the experimental design, and further grouped by differentmolding methods: sham abdominal operation+sham cervical operation group(SO group), sham abdominal operation+drainage of cervical thoracic ductgroup (D group), SAP+sham cervical group (SAP group), SAP+drainage ofcervical thoracic duct group (SD group), SAP+injection of polyphenol acidof Salvia miltiorrhiza group+sham cervical group (SI group), SAP+injectiongroup+drainage of cervical thoracic duct group (SDI group). Each group divided into2h,6h,12h subgroups, and each group contains8rats.The SAP rat model was induced by the retrograde injection of5%sodium taurocholate into biliopancreatic duct. Afterwards the injection ofpolyphenol acid of Salvia miltiorrhiza and(or)the drainage of cervical thoracicduct were conducted according to the different groups. The lymph fromthoracic duct was collected by none-pyrogen Eppendorf tubes and the tubeshould be changed every hour. At the time points of2h,6h,12h after the makeSAP model, rats were executed and blood was collected through abdominalaorta. Then observe the change of organs and collect other specimen. Theblood, lymph, pancreas and liver tissues were processed and tested for alanineaminotransferase (ALT), aspartate aminotransferase (AST), amylase (AMY),catalase (CAT), glutathione peroxidase (GSH-PX) activity in serum,Endotoxin content in plasma and lymph, catalase (CAT) and glutathioneperoxidase (GSH-Px) activity in serum and liver tissues, and pathologicalchanges of pancreas and liver were observed under optical microscope.Results:1At all time points, the pancreas and liver pathological scores, serumALT, AST, AMY content, endotoxin content in plasma, CAT, and GSH-Pxactivity in serum and liver of rats in SO group and D group was no significantdifference (P>0.05);at respective time point, CAT, and GSH-Px activity inserum and liver of rats in SAP group, SD group, SI group and the SDI groupwere significantly lower than that of the SO group and D group (P <0.05),while other indicators were higher than that of SO group and D groupsignificantly (P <0.05).2At respective time point, the pancreas and liver pathologicalscores,ALT, AST, AMY content in serum, endotoxin content in plasma of ratsin SD group, SI group and SDI group were significantly lower than that ofSAP group (P <0.05), while CAT, GSH-Px activity in serum and liver weresignificantly higher than that of the SAP group (P <0.05). 3Compared with the corresponding time point in SD group, pancreaticpathological scores, ALT and AMY in serum of rats in SDI group (2h)decreased significantly (P <0.05), whereas GSH-Px activity in serum and liversignificantly increased (P <0.05); The pancreas and liver pathological scores,ALT, AST, AMY content in serum, endotoxin content in plasma of rats in SDIgroup(6h,12h) decreased significantly (P <0.05), whereas CAT and GSH-Pxactivity in serum and liver increased significantly (P <0.05).4Compared with the corresponding time point in SI group, pancreaticpathological scores,ALT,ASTand AMY in serum of rats in SDI group (2h)decreased significantly (P <0.05), whereas GSH-Px activity in serum and liverincreased significantly (P <0.05); The pancreas and liver pathological scores,ALT, AST, AMY content in serum, endotoxin content in plasma of rats in SDIgroup(6h,12h) decreased significantly (P <0.05), whereas CAT and GSH-Pxactivity in serum and liver increased significantly (P <0.05).5Compared with the corresponding time point in SD group,ALT contentin serum of rats in SI group(6h) decreased significantly (P <0.05),while ASTcontent in serum,GSH-Px activity in serum and liver of rats in SI group (12h)increased significantly (P <0.05);6Except for the non-significance of hepatic GSH-Px activity in SDIgroup between6h12h (P>0.05);the pancreas and liver pathological scores,serum ALT, AST, AMY content, endotoxin content in plasma, CAT,andGSH-Px activity in serum and liver in each group increased graduallyrespectively with time (P <0.05), whereas CAT, GSH-Px activity serum andliver decreased as the time went by (P <0.05).7The AMY and endotoxin content in lymph of thoracic duct of rats in Dgroup show no significant change with time(P>0.05),and was significantlylower than that in the corresponding time point of SD and SDI group (P<0.05).8Compared with the corresponding time point of SD group, the AMYand endotoxin content in lymph of thoracic duct of rats in SDI group weresignificantly lower (P <0.05). 9Compared with the ingredients’ content in the lymph of thoracic duct ofthe same rat, the endotoxin content in plasma of rats in the D group shows nosignificance(P>0.05),while the AMY content in serum increased significantly(P <0.05)；the AMY content in serum and endotoxin content in plasma of ratsin the SD group and SDI Group decreased significantly (P <0.05).Conclusions:1The liver appears evident injury pathological morphological changes,as well as the increase of AST and ALT which are sensitive to the hepaticinjury in the early stage of severe acute pancreatitis of rats,which means thatsevere acute pancreatitis can cause liver injury in the early stage of SAP.2The drainage of thoracic duct lymph or intravenous injection ofpolyphenol acid of Salvia miltiorrhiza can either effectively suppress thepancreas and liver injury during severe acute pancreatitis of rats, and theeffect of the combined intervention is more obvious than a single one.3The possible mechanisms that the drainage of thoracic duct lymphsuppresses SAP-associated liver injury of rats is the decrease in theintestine-derived endotoxin and pancreas-derived enzymes into the bloodthrough the lymphatic pathway, thereby reducing the damage to variousorgans.4The possible mechanisms that the intravenous injection of polyphenolacid of Salvia miltiorrhiza inhibites SAP-associated liver injury of rats is theimprovement of microcirculation,the enhancement of activity of body’santioxidant enzymes, thereby improving the pancreatic and hepatic capacity toresist the damage factors and ameliorating the SAP-associated liver injury.5The content of endotoxin in lymph increases significantly in the earlystage of SAP of rats, and was consistent with the increase of pancreas andliver pathological scores, which means the lymph is an important way of thetransmission of intestine-derived endotoxin.6The content of AMY in serum and lymph increase significantly in theearly stage of SAP of rats, which means the lymph is an important way of thetransmission of pancreas-derived enzymes. 7The activity of antioxidant enzymes (CAT, GSH-Px) in serum and liverdecrease significantly in the early stage of SAP of rats, which results in theimpairment of anti-oxidative capacity. |
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