Effects Of Hedgehog Signaling Pathway Mediated TGF-beta 1 On Pulmonary Fibrosis Induced By Paraquat Poisoning

Background:Paraquat(PQ), which the trade name isl,1’-dimethyl-4, 4’-bipyridinium dichloride, is the herbicide of the bipyridines and is inactive when it contacts the earth. Paraquat is widely used in farming with its cheapness, convenience and better effect than other herbicide. Paraquat is an easy thing to get in China and the poison of paraquat had a highly nember of people because in the early packing there was no symbol of rank poison and no drinking and in the later packing the symbol was just about difficult treatment but no sign of highly death rate and no emetic in liquid such as in USA and Europe. The death rate was reported out home was 40%-50% and in home was 80%. The death dose of paraquat is very little and the concentration of paraquat in blood is opposite to the prognosis. Paraquat was distributed in various such as lung, liver, kidney, thyroid and CNS especially in lung after the absorption in blood, which could lead to the multiple organ failure. Early severe pulmonary effusion, delayed pulmonary fibrosis and lung function failure are the most significant parts of cause of death. The mechanism is still indefinite. The theories of oxygen free radicals and lipid peroxidation injury are the mainstream research, but no theory could explain the entire mechanism of PQ. With the development of cell molecular biology, the role of cytokine network in pulmonary fibrosis is getting more significant and related researches are appearing more. Hedehog pathway palys an important role in embryonic development and there is an relationship in various of cancer and Hedgehog pathway and also the fibrosis especially in liver and kidney. But in lung fibrosis, especially the fibrosis with paraquat poison is little reported.Objective:To observe the therapy of Hedgehog signal path in paraquat-induced acute lung injury and pulmonary fibrosis rats models.Method:30 adult healthy Wister male rats were randomly distributioned to three groups. The frist group was lavage of paraquat and intraperitoneal injection with NS, the second group was lavage of paraquat and intraperitoneal injection with Gant61, the third group lavage of NS and intraperitoneal injection with NS(the paraquat poisoning at the beginning and rats were intragastric administration paraquat dissolvent 50mg/kg body weightsiological salin). At 1th,3th,7th,14th,21st,28st day rats were sacrificed, sample lung tissues were collected to detect the express of TGF-B1, ERK,, JNK and P38 with Western Blog, TGF-β1, ERK, P38 with immunohistochemical staining, TGF-β1 with PCR and pathology with HE staining.Result:The level of TGF-β1, ERK, JNK and P38 is higher, and the poison group has a higher level than control group with Gant 61. The same in the immunohistochemical staining with TGF-β1, P38.Conclusion:Hedgehog pathway is involved in lung fibrosis with paraquat poison.