The Study Of Using TGFB-1Antibody Treat Acute Lung Injury Induced By Paraquat

Background:Paraquat is a kind of highly efficient quaternary amine herbicide.Since it’s excellent weed control effect and poor price, paraquat is widely used in ample agriculture country. But for it’s high toxicity to people, and there are no specifics,paraquat poisoning has become the highest humans mortality in acute poisoning by herbicide. Paraquat poisoning can cause lung, liver, kidney and other organ damage, and lung is the most serious damage organ [1]. Paraquat poisoning has become the common severe acute disease in poisoning in the department of internal medicine. The mechanism of the acute lung injury in paraquat poisoning is not clear,and the significance about paraquat poisoning research in basic and clinical is clear. In previous study, Scientists often focused the mechanism on active oxygen and lipid peroxidation in lung injury induced by paraquat poisoning, but the focus has been shifted to the changes of cytokines with the development of pulmonary fibrosis mechanism in recent years.It’s believed the bad repairment is the main mechanism of pulmonary fibrosis. Lung macrophage phagocytose dead cells and pathogens,and inducing inflammation classically,then macrophage induces the TGF-pi. TGF-β1is a multifunctional cytokine,and is the key cell factor of fibrosis.Previous researchs suggest Smads pathway,downstream of TGF-β1,is the primary channel to TGF-β1effection.,and Smad2,Smad3,Smad4have a major role in this channel. With the progress of the MAPK signal channel in recent years, especially in the Ras/Raf/MEK/ERK signal channel mechanism and it’s biological effect, the role of ERK/MAPK signal channels in pulmonary fibrosis gradually got the attention. Smad proteins and ERKproteins and other signal channel has a reciprocal interaction and constitute a complex network.It’s believed that the network play an important role in the process of pulmonary fibrosis. Mr. Jian Xiangdong suggested that TGF-β1antibody will be able to become the more effective treatment about paraquat-induced lung injury, but without the experiment confirmed.Objective:Our research study the therapy of TGF-β1antibody in treating acute lung injury and pulmonary interstitial fibrosis induced by paraquat.Method:All90adult Wister male rats were randomly assigned to three group: paraquat poisoning group, the TGF-β1antibody therapy group and the control group o The paraquat poisoning group(rats were intragastric administration paraquat50mg/kg body weight once at the beginning); the TGF-β1antibody therapy group(rats were given TGF-β1antibody0.lmg/kg Subcutaneous injection30minutes after paraquat was given, then the same dose was given once a week);the control group(rats were intragastric administration with physiological saline). At7th,14th,21st,28th day rats were sacrificed postanesthetic respectively after paraquat exposure, sample of lung tissue and bronchoalveolar lavage fluid were collected. TGF-β1、 ERK1/2and P-ERK of the sample were determined. Optical microscope were performed to examine pathological changes in lung. And observe the experiment animal behavior closely.Results:The dosage of TGF-β1、ERK1/2、P-ERK and hydroxyproline of paraquat poisoning group were significantly higher than the same of the control group, and the paraquat poisoning group was significantly higher than the therapy group in the same time. Under optical microscope, the tissue damage of lung was aggravated, and reduced after TGF-β1antibody was administrated. The paraquat poisoning group rats’ activity appear decreased and spiritual malaise, mouth and nose bleeding,part of rats breathing difficulties because of lack of oxygen, the therapy group rats reaction significantly reduce to the poisoning group rats in the same time, after five to seven days,time poisoning group rats’activity were gradually increased, the oxygen to relieve symptoms release significantly.Conclusion:ERK signaling pathway are involved in pulmonary interstitial fibrosis induced by paraquat poisoning pathogenic processes, TGF-β1is a key factor in the two pathways, In this experiment the TGF-β1antibody has therapeutic effect on acute pulmonary injury,which induced by paraquat poisoning.