Experimental Study Of TGFβ1-Smad Signal Path In Paraquat Induced Acute Lung Injury

Background:Paraquat, the trade name for1,1’-dimethyl-4,4’-bipyridinium dichloride.It’s function as weeding was found at1960s. It has became one of the most widely used herbicides in developing countries in recent30years. The number of people who attempt to suicide or accidental poisoning is still high because the more chance to exposure. Most cases of paraquat poisoning result from intentional ingestion, but it can also be absorbed through skin and respiratory inhalation. It is highly toxic to humans and is responsible many cases of acute poisoning. After intaked, it rapidly distribute in the lung, liver, kidney and muscle, etc,mainly in the lung and skeletal muscle.So the major target organ is lung, acute lung injury and advanced pulmonary interstitial fibrosis is the most serious complication. The mechanism is still indefinite, the present study include the theory of oxygen free radicals, lipid peroxidation injury, cytokines and DNA damage, but there is no theory can explain the mechanism of PQ induced lung damage detailedly. In recent years, with the development of cell molecular biology, the role of cytokine network in pulmonary fibrosis get the attention of people, then the research about this increased. TGF-beta1has been acknowledged as the promoter in the formation and development of fibrosis, it depend on the Smad and ERK signal channel. Scholars have confirmed that TGF-beta1play an important role in the formation of pulmonary fibrosis in PQ poisoning rats model and patients. But there is little research on whether the TGF-beta1depend on Smad signal path in the process of PQ-induced pulmonary fibrosis. Objective:To observe the therapy of TGFβ1-Smad signal path in paraquat-induced acute lung injury and pulmonary fibrosis rats models.Method:80adult healthy Wister male rats were randomly distributioned to two groups, the paraquat poisoning gro at the beginning); control group(rats were intragastric administration with phy up(rats were intragastric administration paraquat dissolvent50mg/kg body weightsiological saline). At7th,14th,21st,28st day rats were sacrificed, sample lung tissues were collected to detect the express of TGF-β1、 TBR I、Smad、Col I、TIMP1and MMP2in lung tissues by immunohistochemical staining, TGF-β1in lung tissue by ELISA. Optical microscope was performed to examine pathological changes in lung tissues with HE and Masson staining.Result:The TGF-β1、TBR I、Smad4、Col I、TIMP1and MMP2in paraquat poisoning group were significantly higher than control group. The TGF-β1、TBR I Smad4and Col I reach the peak at14th. MMP2reach the peak at7th, then decline. TIMP1reach the peak at21st. Under optical microscope, the tissue damage of lung of poisoning group was aggravated with exposure period.Conclusion:The TGFβ1-Smad signal path may play an important role in the development of paraquat-induced acute lung injury.