The Protective Effect Of Xuebijing Injection Combined With Dexamethasone On Rats' Acute And Chronic Pulmonary Injury Induced By Paraquat

Background and Objective Paraquat(PQ) is a quarternary nitrogen herbicide widely used for broadleaf weed control.As lung is rich of oxygen in human body, and alveolus have a amine like matter transferring system,so that lung is the primary injuried target organ.If human take orally a great volume of PQ solution,he would occur acute PQ poisoning(APP),which show acute pulmonary edema, blooding and multiorgan function failor withen 24 hours,and that lead to a much high mortality. On the contrary,if one take orally a little of PQ, the early respiratory symptom is not evident or be mild. The patient would neglect its severity and delay in asking for a treament easily.Because a major part of PQ is cumulated in lung and muscle, and its excretion is very slow.The toxicity exist persistently and form into inreversible pulmonary fibrosis gradually.Then the patient would occur dyspnea progressively, even being dead one month later. The chronic pulmonary fibrosis is a common mortal pathogeny except for acute multi organ failor and pulmonary blooding in early PQ poisoning. So we would actively prevent acute pulmonary blooding ,edema and chronical pulmonary fibrosis to improve living status and deduce the mortality. To date there is no selectively antitoxic agent,the traditional treatment is antioxidation and inhibitting immunoreaction.Even under actively treatment condition,the mortality would be as high as 50-70%. XueBijing injection is Chinese patent medicine preparation which is consist of Danshen, Chishao,Chuanxiong,et,al.It can clear out oxygen free radical,modulate immunoreaction.Recently,there are much laboratory and clinical experiments about evaluating its effect on PQ posinoing,such experiment outcome show some positive effect.We will use XueBijing injection and which combined with dexamethasone to treat acute PQ lung injury(ALI) and chronic pulmonary injury induced by PQ,to explore the protection effect and mechanism by measure IL-6,TGF-β1,SOD,MDA and HYP level, provide a theory base for clinical practice.Methods (1)The first experiment :Seventy-five male Wistar rats are divided into five groups randomly, apart from normal group(A) using saline, model group(B) and treatment groups are given 20%PQ(20mg/Kg.ip),after 2h,except that the normal and model group are given saline as treatment control, treatment groups Are administered with Xuebijing injection(C)(2.5g/Kg),(D)(30mg/Kg),Xuebijing injection combined with dexamethasone (E),One time once day till being killed. At d2,d3,d4 after being poisoned,five rats in each group are killed, level of SOD,MDA,IL-6 in serum are measured, pulmonary coefficient and pathology change are observed too.(2)The second experiment: Thirty male Wistar rats are divided into six groups randomly, apart from the normal group(A) using saline, model group (B)and treatment groups are poisoned by paraquat (16mg/Kg.ip).after 2h,the treatment groups are administered with little dosage of Xuebijing(C)(1.25g/kg),great doseage of Xuebijing(D)(2.5g/Kg),dexamethasone (E) (25mg/ Kg),great dosage of Xuebijing combined with dexamethas- one(F),the normal and model groups are administered with saline, the treatment are performed once a day and continued for 4days.At d28 after PQ injection, five rats in each group are killed respectively,serum TGF-β1 and lung tissue HYP level are measured, pulmonary coefficient and histological change are observed too.Results (1)The first experiment outcome:Observe common state: B group rats seemed dispirited, moving tardy, mouth and nose blooding .The treatment group toxicity symptom is mild, E group is the best.Lab test:Compared with model group, treatment groups have higher level of serum SOD at d3,d4, E group is the highest and better than C,Dgroup;Treatment groups'MDA level is less than B group, and E group is the least at d4;Each treatment group's IL-6 level is lower than Bgroup, and E group is the lowest. Treament groups'pulmonary coefficient is less than B group,and E group has is the least.At d3,treatment groups have higher PO2 and lower PCO2 than Bgroup, and Egroup is the best.Above differences are all statistically significant(p<0.05).lung overview:A group rats'lung look pink, elasticity; B group look edema and dark red,a great area of blooding;Each treatment is not as serious as B group ,and E group is the mildest.Lung pathology:A group's alveolus structure is integrity,has no effusion.Bgroup is blooding in alveolus with inflammation cell effusion.The treatment groups'lung injury is mild,and the E group is the mildest. (2)The second experiment outcome: Bgroup occurred mouth and nose blooding two days later, reject taking food,body weigh not increased normally,improved retardly.Each treament group have a mild blooding ,and began to improve four days later,the body weight increased relatively quick,among them,Fgroup showed the best. In the treatment groups, the levels of serum TGF-β1 and lung tissue HYP are less than that of B group, among the treatment groups,F group is the best, and D,E group is middle. Above differences are all statistically significant(p<0.05).Compare lung coefficient within them,Fgroup is the best,others have no fifference statistically.The B group histological show pulmonary fibrosis, treatment groups'pulmonray fibrosis are less serious, among them F group is the mildest.Conclusion Xuebijing injection and dexamethasone both can inhibit IL-6, TGF -β1and lipid super oxygenization, inhibit fibroblast's migration and activation.Decrease the MDA and HYP value, protect SOD activity, alleviate acute pulmonary blooding ,edema and chronic pulmonary fibrosis.Both of them have similar effect.By combination,they could exhibit stronger protection by actting on multi target sites.