Dissertation
Dissertation > Medicine, health > Internal Medicine > Systemic disease > Poisoning and chemical damage > Drug-induced diseases

Study on the expression of TNF-a and ICAM-1 during low dose aspirin induces rat gastric mucosal injury

Author ZhangWei
Tutor WuBenZuo
School Postgraduate Medical School
Course Geriatrics digestion
Keywords Aspirin Gastric mucosal injury TNF-a ICAM-1
CLC R595.3
Type Master's thesis
Year 2001
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OBJECTIVE: ① To establish a model of gastric mucosalinjury with low dose aspirin of 5.021mg/kg. ②To studywhether low dose aspirin can induce gastric mucosal injuryand whether low dose aspirin is dangerous to gastrointestinaltract. ③To investigate whether the expression of TNF-a andICAM-1 in the rat gastric mucosal cells participates in thepathogenic mechenism of gastric mucosal injury induced bylow dose aspirin and its significance.METH0DS: A model of gastric mucosal injury with low doseaspirin of 5.021mg/kg (corresponded to a man of 60kg bodyweight taking 50mg aspirin every day) was replicated on thebase of routine dose aspirin (75mg/kg). The condition ofgastric mucosal injury was observed. Then we examinedthe expression of TNF-a and ICAM-1 protein and mRNA ongastric mucosal cell in SD rats with aspirin byimmunohistochemistry and RT-PCR methods.RESULTS: ①Gastric mucosal injury occurred in experimentgroups at the third day after administration of low doseaspirin of 5.021mg/kg and the injury index is 9.11±0.62.Gastric mucosa injury arrived at peak level at the fourteenthday and the injury index is 23.52±0.53. ②Gastric mucosalinjury appeared in 40 rats among total 48 rats in experientgroups after administration of low dose aspirin. The ratio was83.3%. ③Disperse erosion and hemorrhagic dot can be foundat the gas tric mucosal surface under the anatomic microscopeafter admini s trat ion of low dose aspi rin in experiment groups.The mucosa 1 injury 1ocated in gas tr ic corpus and para 11ed wi thgastric vertical axis. @ In histopathology afteradministration of 1ow dose aspirin we can find that theepi the1 ias cel l s denatura1 izated and some ce1ls fal1ed off.Eros ion and effus ion can be found. There was congest ion andoedema in gastric mucosa. The glands was dainaged. @Thereare some changes under the scaning e1ectriC microscope afteradministration of aspirin. The mucus layer got thin. Thereare dispersed and di 1apidated mucosal surface layer cel1s.The g1andu1ar cel ls break off. The epi thel ias exfol iate inpart areas. @After administration of low dose aspirin byinununohi s tochemi s try method, the resu1 ts showed that TNF--abegan to express at the third day, peaked at the forteenthday, dec1 ined at the twenty--first day, a l it t1e express ionat the the twenty--eighth day and the thirty--fifth day inexperiment group; ICAM--1 began to express at the third dayafter administration of 1ow dose aspirin, peaked at thetwenty--first day, expressed 1 it t 1e at the twenty--eighth dayand the thirty--fifth day. The express ion of TNF--a and ICAM--1decreased significant1y after administration of aspirincompared with that before administration of aspirin inexperiment group. There is 1ower express ion in control groupthan in experiment group. There is no obvious difference amongcontro1 groups. @The injury index enhanced gradua11y in thesame time when the expression of TNF-- a and ICAM--1increased. TNF-- a and ICAM--1 show pos i t ive corre1a t ion. Thecorre1ated index was 0. 972 and 0. 810 respect ive1y. TNF-- a andICAM--1 had c1ose relat ion wi th gastric mucosal injury.C0NCLUSI0NS: O A mode1 of gas tric mucosal injury wasrepl icated wi th low dose aspi rin of 5. 021mg/kg successfu11y.@Low dose aspirin may induce gas tric mucosal injury and 1owdose aspirin has some dangers on gastric mucosa. @ Theexpres s ion of ICAM1 and TNF--a p1ays an important ro1e in themechani sm of 1ow dose aspi rin--induced gas tric mucosal injury.

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