| Obstructive jaundice leads to kinds of complicated and seriouspathophysiologic changes. Bile reflux into blood due to enlargedintrohepatic biliary ducts and damage of hepaticprotein-synthesizing ability deteriorates hepatic function, evenfailure. Decline in local intestinal immunity due toendotoxemia ,intestinal bacterial translocation (IBT) due toimpaired intestinal barrier, and higher occurrence of digestive ulcerlead patients to deteriorated, even death. This study is designed ,byrats with obstructive jaundice, to explore the morphological andfunctional changes in liver, the mechanism of impaired physicaland local immune barrier in ileum, the pathophysiologic variationsin epidermal growth factor(EGF) ,and the influence of growthhormone on all of them.Methods60 healthy Wistar rats of both sexes were randomly dividedinto sham-operated (15 rats, Group A), common biliaryduct-ligated, (15 rats, Group B), bile duct-ligated plus rhGH-treatedfor 1 week (15 rats, Group C) and bile duct-ligated plusrhGH-treated for 2 weeks (15 rats, Group D).All procedures were performed aseptically under generalanaesthesia using intraperitoneal thiopentone (0.25%,25 mg/kg).The middlemost abdominal incision was made. In Group A(the sham group), the rats had a similar incision followed bymobilization of the common bile duct (CBD), without ligation ordivision. In group B rats, the common bile duct (CBD) wasidentified, mobilized, doubly ligated using silk. In Group C andGroup D rats, the similar procedures were performed,followedrhGH-hypodermic injection(0.75U/Kg/day) for 1 week, 2weeks,respectively.All animals had free food intake pre-and post-operation.Group A and Group B rats were killed 2 weeks after procedures.Group C and Group D rats were aseptically killed at the end of the1st week, 2nd week,respectively.And the sample of bloodserum,liver, mesenteric lymph nodes, stomach, ileum as well asgastric and intestinal juice were harvested.Liver, stomach, and ileum tissue were histopathologicallyanalysed. Hepatic pathology were studied.The thickness ofmembrane and the height of villi in stomach and ileum weredetermined. Serum levels of total bilirubin (TB), alanineaminotransferase (ALT), prealbumin (PA), insulin-like growthfactor-I(IGF-I) were measured. Mesenteric lymph notes(MLNs)were squeezed and cultured. SIgA as well as epidemic growthfactor(EGF) level in gastric and intestinal juice were measred.ResultsNaked-eyed observation, 2-3 days after CBD ligation, rats'skin in ear-tip and tail became yellowish, and urine turnedyellow.With time on, 4-6 days later, obvious jaundice wasnoted,indicating the ideal model of obstructive jaundice. Peritonealobservation, 1 week after procedure, liver was found swelling upand brightless. Common biliary duct was remarkably dilated. CBDwall became thin and bile juice became thicker. Bowels lookedyellow and mesenteric lymph nodes showed enlarged.Liver histologic observation showed a unvaried microstructureof lobule and portal region in Group A. In Group B, obviouschanges in liver microstructure were shown—multiple necroticspots and patches, enlarged intrahepatic ducts, enormouspsudo-hepatic ducts formation , abundant inflammatory cellularinfiltration and fibrous hyperplasia.In Group C and Group D,similar, but slightly-degreed changes were found.Stomach histology. Compared with group A,mucousmembrane in Group B rats became thinner, villi became shorter inlength and sparse.No peptic ulcers were found.Ileum histology. In group A rats, uninfluenced ileum villicould be seen. Intestinal wall was even in thickness and membranaserosa kept intact.In group B, however, rats had thinner intestinalwall with shorter villi (Group B: 158.1±22.4μm v.s Group A:253.5±38.6μm,P<0.01), and thinner mucous membrane (GroupB: 232.4±21.5μm v.s Group A: 362.2±42.8μm,P<0.01). Ingroup C and D rats, microstructure of villi and mucous membranewas comparatively normal, with only mild edema in the villifundus and prolonged villi (Group C and D: 216.3±28.6μm,232.5±30.1μm v.s Group B: 158.1±22.4μm, P<0.05), andthickened mucous membrane (Group C and D: 308.5±33.6μm,334.0±43.4μm v.s Group B: 232.4±21.5μm, P<0.05).With application of growth hormone, sIgA level in intestinaljuice had been increased apparently (Group C and D: 114.4±18.4μg/L,126.4±16.8μg/L v.s Group B: 70.2±13.5μg/L, P<0.05).It demonstrated that rhGH can well recorrect morphologicalalteration caused by obstructive jaundice in liver, can remarkablyaccelerate the recovery of damaged protein-synthesizing functionof hepatocytes. Still, by maintaining integrality of intestinalepithelium,as well as, by increasing synthesis and secretion of sIgAin ileum epithelium, rhGH can strengthen physical and immunebarrier in ileum, leading to a lower IBT in rats.The ratio of IBT inascites and mesenteric lymph nodes decreased from 25.0%(3/12)and 41.7%(5/12) in Group B to 13.3%(2/15), 20.0%(3/15) (GroupC) and 7.1%(1/14), 14.3%(2/14) (Group D),respectively.2 weeks after CBD ligation, Serum level of TB and ALP of ratsincreased apparently (115.7±20.6μmmol/L,356.2±48.3IU/L inGroup B v.s 7.5±2.3μmmol/L,82.4±10.5IU/L in GroupA,respectively, P<0.01). With administration of rhGH, Serum levelof TB(93.6±13.5μmmol/L in Group C v.s 108.4±18.1μmmol/LGroup D, respectively, P>0.05) and ALP(284.2±43.2IU/L inGroup C v.s 293.8±59.5IU/L in Group D, respectively, P>0.05)deceased slightly, but were still far higher than that of Group A. Inrats with obstructive jaundice,hepatic protein-synthesis abilitydecreased remarkably, and serum level of PA decreased (126.6±30.7mg/L in Group B v.s 258.8±36.4 mg/L in Group A, P<0.01).With treatment of rhGH, serum level of PA(162.4±33.3mg/L inGroup C, 183.1±42.2mg/L in Group D,respectively, P>0.05)increased, but was far lower than that of Group A. The resultsrevealed that with 1-2 week of administration of rhGH,damagedhepatic function in rats with obstructive jaundice can only bepartially restored.Insulin-like growth factor-I (IGF-I) is an importantintermediate when rhGH takes effects. Its serum level decreasedobviously in rats with obstructive jaundice (612.9±121.5 mg/L inGroup B v.s 926.4±203.3 mg/L in Group A, P<0.01), whichdemonstrated a lack of rhGH in rats with obstructive jaundice.When rhGH was manually given, serum concentration of IGF-I inrats increased (732.8±137.2 mg/L in Group C v.s 746.3±150.8mg/L in Group D, respectively,P>0.05), but still far lower than thatof Group A.In this study, it was also proved that the concentration of EGFin gastric juice and intestinal juice in rats with obstructive jaundicedecreased (0.92±0.12μg/ml in gastric juice, 2.25±0.25μg/mlintestinal juice, in Group B, and 1.13±0.12μg/ml in gastric juice,5.88±0.96μg/ml intestinal juice, in Group A. P>0.05, P<0.01respectively). It showed that probably due to damaged morphologyand function in liver and intestine in rats with obstructive jaundice,the absorption and the application of some immune nutrients, suchas glutamine and so on, were hampered ,and EGF production andsecretion from Brunner's gland in gastroenteritic tract decreased. InOJ rats, EGF level in intestinal juice decreased remarkably, whichdemonstrated that EGF in intestinal epithelium was more easy tobe eliminated and exhausted. With administration of rhGH, EGF ingastric juice increased slowly (1.06±0.22μg/ml in Group C v.s1.12±0.25μg/ml in Group D,P>0.05), but increased statisticallyin intestinal juice (3.54±0.66μg/ml in Group C v.s 4.09±0.82μg/ml in Group D). It demonstrated that Brunner's gland in intestinewas probably well influenced by rhGH given ,so as to produce andsecrete much EGF. With growth hormone administration, anelevated EGF in gastric juice would play an important role inproliferation and recovery in gastrointestinal epithelium to preventstress ulcers.In rats with obstructive jaundice, a decreased EGFconcentration in gastric juice hints the probability of stress ulcer.However, in this study, stress ulcer had not been found in gastricmembrane. This is probably relevant to a short term of duration ofobstructive jaundice and light degree of jaundice. With rhGHadministration, an elevation of EGF concentration in gastric juicerevealed that growth hormone could intensify the function ofBrunner's gland in gastrointestinal tract and make them produceand secrete much EGF to prevent the occurrence of digestiveulcers.ConclusionThis study shows: 1) Obstructive jaundice can lead toabnormal morphology of rat liver, such as necrotic spots or patches,inflammatory cellular infiltration and fibrous hyperplasia,anddeclination of liver function,such as enzyme changes in serum andpoor protein-synthesis ability. Growth hormone administration canalleviate the number and the degree of necrotic spots in liver andimprove these pathological changes. 2) Obstructive jaundice in ratscan decrease the thickness of ileum epithelium and the height ofvilli, can make the physical barrier damaged and lead to IBT. WithGH administration, integrity and permeability of intestinalepithelium can be improved. GH shows a protective effect onphysical barrier in intestinal tract. 3)In obstructive jaundice,without biliary salt entering intestinal ducts, maturation of T lymphcells is hampered, and plasma cell secretes less sIgA. Meanwhile,sIgA from biliary ducts reflux back into blood, which makes theconcentration of sIgA in ileum juice decrease remarkably as well asdecreased local immune barrier function in intestinal tract. WithGH administration, an elevation of content of sIgA in intestinaljuice strengthens intestinal immune barrier function. 4)Inobstructive jaundice, mainly because of damaged physical andimmune barrier function, IBT increases. With GH administration,IBT decreases due to improved barrier function. 5)In obstructivejaundice, a drop of EGF concentration in gastrointestinal juice(more remarkable in intestinal juice) predicts poor protection ongastrointestinal membrane exerted by EGF and the probability ofdigestive ulcer. With GH administration, the EGF concentrationcan be elevated and digestive ulcer can be well prevented.
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