| Objective Obstructive jaundice (OJ) is the commonpathological course of many diseases in hepatobiliarysurgery. The treatment of OJ is difficult all along .Infection , hypohepatia , even systemic inflammatoryresponse syndrome(SIRS) or multiple organ dysfunctionsyndrome (MODS) often happen after operations, so theprognosis of patient is usually not good .OJ does harm to the body in many ways, but themechanisms of OJ are not very clear till now. Recent studiesshow that OJ is related to cytokines, inflammatory factorsand endotoxemia which play a main role in postoperationcomplications, high mortality and inhibition of manyfunctions of the body. Obstruction of biliary duct leads todecrease of biliary salt which can inhibit generation ofbacterias, decomposes endotoxin and disrupts intestinalbarrier function, and which results in intestinal endotoxemia.Endotoxin can promote the secretion of tumor necrosisfactor-α(TNF-α), an important factor secreted bymacrophage, which leads to immunodepression. Thus, underthe pathologic status, it causes patients fever, shock andMODS, so a vicious circle forms. In addition, hepatocellularapoptosis takes place in the process of OJ, some researchshows that hepatocellular apoptosis increased with theextension of obstruction time, then induces more lesion ofhepatic function. Besides that, some investigations find thatpathologic hepatocellular apoptosis directly relates to TNF-α,however, the mechanism is not elucidated nowadays.Glycine, a kind of natural polar and non-essentialamino acid, consists of an amino group and a carboxyl group,which not only participate protein metabolism as basicfunction but acts as an inhibitory neurotransmitter in centralnervous system, although which is usually considered as atrivial amino acid providing nitrogen to other proteins inother tissues. But studies in current years illustrate thatglycine takes effect on anti-inflammation, immuneregulation and cell protection. Studies show that glycine iseffective on the treatment of shock, alcoholic hepatitis,hepatic cirrhosis, arthrositis, acute necrotizing pancreatitis,tumor, and drug poison, especially in ischemia reperfusioninjury. Nevertheless, few is reported about the effect ofglycine on OJ. The mechanisms include: 1. to decreaseinflow of calcium by activating glycine receptor onmacrophagus and prevent excessive activation ofmacrophagus, finally to reduce the release of toxicfactors(mainly TNF-α);2. to reduce the lesion of hepaticcells via modulating calcium channel;3. to decrease bloodconcentration of intestinal endotoxin possibly by inhibitingdegranulation of mastocyte, reducing the release ofhistamine and permeability of intestinal tract. The lesioncaused by OJ happens in the way of 'intestinalendotoxin—macrophogus—TNF-α',therefore, in abstracto,glycine can moderate the lesion caused by OJ in manyaspects. The aim of this study is to observe the effect on theTNF-α in serum of the rats and the hepatocellular apoptosiswith obstructive jaundice cured by glycine.Method The 54 adult male Wister rats were dividedinto three groups randomly and averagely: the shamoperation group, normal control group and treatment group,then every group was subdivided into three groupsaccording to time point at 7,14,21d after operation. Thesham operation and normal control group were fed bynormal diet and water and the treatment group was fed bynormal diet and 5% glycine solution 5 days before theoperation. All rats were anesthetized by 1% pentobarbitalsodium by intraperitoneal injection, fixed on operation table,sterilized by iodophors and operated. In sham operationgroup hepatic funiculus was isolated, but ligated and cut innormal control group and treatment group. After operationsamples were taken at presumptive time point.Results The level of TNF-α in the serum and the indexof hepatocellular apoptosis in each time point are notobviously changed in sham operation group, but in normalcontrol group and treatment group is significantly higherthan in sham operation (P<0.01=, what's more, the levelis positively correlated with the period of obstruction.Moreover, the level of TNF-α and the index ofhepatocellular apoptosis in treatment group are lower thanthe normal control group(p<0.01=. Liver samples wereobserved under light microscope, and few differences wasfund at each time point, but found in normal control groupand treatment group. In normal control group, at 7d thereappeared the apoptosised hepatocellular , punctiformnecrosis of hepatocytes, slight proliferation of fibrous tissue,scutellate necrosis in some areas, irregular arrangedhepatocytes and bile embolus in hepatic sinusoid;at 14d there appeared a lot of apoptosisedhepatocellulars ,multi-shaped necrosis surrounded byinflammatory cells, massive proliferation of fibrous tissueand small bile duct;at 21d there appeared the apoptosisedhepatocellular obvious proliferation of hepatic tissue,cirrhosis-like disordered structure and wide necrosis. Intreatment group, at 7d there appeared the apoptosisedhepatocellular, punctiform necrosis of hepatocytes, slightproliferation of fibrous tissue, no scutellate necrosis;at 14dthere appeared the apoptosised hepatocellular and exitedhepatic lobule surrounded by few inflammatory cells andslight proliferation of fibrous tissue and small bile duct;at21d the pathological changes were also slighter than normalcontrol group at same time point.Conclusion The level of TNF-α in the serum andhepatocellular apoptosis are obviously enhanced with OJand positively correlated with the period of obstruction.Glycine, applied preoperation and postoperation, can reducethe pathological changes degree of obstructive jaundice,effectively lower the level of TNF-α and hepatocellularapoptosis ,so it can obviously improve the prognosis of OJ.This conclusion hints that the early use of glycine to patientswith OJ and getting rid of the factors of obstruction activelyat the same time may get favourable curative effect. And as acommon, inexpensive and atoxic medicine, we recommendglycine to be widely applied on the treatment of OJ in clinic.
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