Expression Of Protein Tyrosine Phosphatases SHP-1 In The Lung Of Athmatic Mice And Its Correlation With Airway Inflammation

ObjectivesTo investigate the expression of protein tyrosine phosphatases SHP-1 in the lung of asthmatic mice and its correlation with airway inflammation.MethodsTirty Clean female BALB/c mice were randomly divided into control group and asthma group,protein tyrosine phosphatases inhibitor sodium orthovanadate(sov) group.Chronic asthmatic models were established by ovalbumin(OVA)-sensitization of intraperitoneal injection with OVA aluminum hydroxide gel solution on day 0 and 14 once every other one day and were challenged repeatedly via the airways with inhalation of OVA for 30 days(from day 15 to 45)using ultrasonic nebulization once every other one day.The control group was established by saline as the substitution of OVA of intraperitoneal injection and repeated inhalation of saline as the substitution of OVA. The SOV group were established by the same methods as the asthma group in the early periods,but only in the last week before the mice were killed,they were injected SOV every day before inhalation OVA.The mice were killed after the final antigen challenge.Asthma symptoms were observed.The pathological changes of the lung tissue dyed with HE stain were observed through light microscope at the same time. Cell in bronchoalvoelar lavage fluid(BALF)were counted and classified and the morophological changes in airway were assessed.Cytokines IL-4 in BALF and OVA-challenged IgE in mice serum were determined using enzyme linked immunosorbent assay(ELISA).The level of IL-4R were detected by immunohisto-chemistry.The level of SHP-1mRNA in lung tissues were measured by reverse transcriptase-polymerase chain reaction assay(RT-PCR).ResultsThe asthmatic group appeared the symptoms of chronic asthma,such as scratching the head continuously,breathing fast and deeply,hypokinesia ordysphoria, anorexia,bowing the back,hair messy,abdominal muscle twitching,urinary and fecal incontinence and so on.The Sov group are more seriously.There were more leuko-cytes and eosinophils in the BALF of asthmatic group.In BALF the levels of IL-4 and the serum levels of OVA specific IgE were significantly elevated in the asthmatic group and Sov group,as compared with the control group.The pathological changes of the lung tissue were observed that in asthmatic mice,inflammatory cell increased. The goblet cell hyperplasia,mucus plugs formation in bronchiole,bronchial wall thicken-ing and smooth muscle cell proliferation were much more serious in asthmatic mice and Sov group mice than in control mice.Total BALF inflammation cell,Eosnophils and IL-4R from asthma group and SOV group were significantly higher than those in control group.(p<0.05,respectively),SHP-1mRNA was decreased remarkably in asthma group and SOV group which compared with that of control group (p<0.05, respectively).There were two negative correlations,the one was SHP-1 mRNA and IL-4R,the other was SHP-1mRNA and total cell.Total BALF cell and IL-4R from asthma group and Sov group were significantly higher than those in control group(p<0.05,respectively),SHP-1mRNA was decreased remarkably in asthma group and Sov group which compared with that of control group(p< 0.05, respectively).There were two negative correlations,the one was SHP-1mRNA and IL-4R,the other was SHP-1mRNA and total cell.ConclusionsThis successful chronic inflammation mouse asthma model may be copy by lower-dose antigen-stimulated repeatedly and long time.SHP-1 may be involved in airway inflammation which by down regulated inflammation cell and the level of IL-4R.