ObjectiveTo establish paraquat (PQ)-induced acute respiratory distress syndrome (ARDS) mice model via gavage, in order to simulate oral adminitration in clinical situations.MethodsSeventy-eight 6-8-week-old, specific pathogen free female C57 mice were chosen in this study. The mice were randomly divided into the control group (n=6) and the PQ model group(n=36); the mice in the latter group were randomly divided into 6 poisoning model subgroups further, with 6 mice in each, to find out the suitable concentration of PQ to establish stable ARDS model. The mice in the control group were given phosphatebuffer saline (PBS) by gavage, 200 μL per mouse; while the mice in the 6 poisoning model subgroups were given PQ with varies doses of 3, 10, 30, 100, 150, 300 mg/kg respectively by gavage. The clinical manifestations were observed for 7 days, and the ratio of lung wet/dry (W/D) was measured. After the suitable concentration of PQ for stable ARDS mice model was found, the other 36 mice were randomly divided into the controlgroup and the poisoning model group, both were divided into 4 subgroups, according to different observation point in time (1 day and 2, 3, 4 days after PQ gavage). The mice in the 4 control subgroups (n=3) were given PBS by gavage, 200 μL per mouse; while the mice in the 4 poisoning model subgroups (n=6) were given PQ with the suitable concentration for ARDS mice model by gavage. Pathological manifestations by Haematoxylin-Eosin staining and lung injury score were observed and analyzed.ResultsThe mice began to die at the PQ dosage of 150 mg/kg; while the death rate was stable at 300 mg/kg. On the 2nd and 4th day after PQ gavage, lung W/D was 5.335, 6.113, and 5.525, and 6.403, respectively in the mice in 150 and 300 mg/kg subgroup, which differed much from those in the control group (P<0.001). Congestion, edema, hemorrhage, alveolar structure damage, inflammation cells infiltration of lung tissue were observed, and lung injury score increased.ConclusionPQ-induced ARDS mice model by gavage is established successfully.
Objective To investigate the mechanismof lung injury caused by paraquat poisoning by observing the changes of fibrogenic cytokines in acute paraquat poisoned rats and the effects of pyrrolidine dithiocarbamate ( PDTC) . Methods Sprague-Dawley rats were randomly divided into three groups, ie. acontrol group ( n =6) , a PDTC group ( n =36) , a paraquat group ( n = 36) , and a paraquat + PDTC group( n =36) . The rats in the PDTC group, the paraquat group, and the paraquat + PDTC group were subdivided into 6 subgroups sacrificed respectively on 1st, 3rd,7th,14th, 28th and 56th day after the treatment. The levels of transforming growth factor-β1( TGF-β1 ) , platelet-derived growth factor ( PDGF) , insulin-like growthfactor-1 ( IGF-1) in serum were measured. Meanwhile the expression of connective tissue growth factor ( CTGF) and hydroxyproline in lung tissues were detected. The relationship of above cytokines with hydroxyproline was analyzed. Results The destructive phase in early ( 1 ～7 d) was characterized by hemorrhage, alveolar edema, and inflammatory cell infiltration. The proliferous phase in later stage ( 14 ～56 d) was characterized by diffused alveolar collapse with fibroblast proliferation and patchy distribution of collagen fibers. Compared with the control group, the level of TGF-β1 on all time points, the level of PDGF from7th to 56th day, the level of IGF-1 from3rd to 56th day in the paraquat group all significantly increased ( P lt;0. 01) . Immunohistochemistry results showed CTGF positive cells mainly located in aleolar epithelialcells, endothelial cells,macrophages in early stage, and fibroblasts were main positive cells on the 28th and the 56th day. The expression of CTGF in the paraquat group increased gradually compared with the control group on different time points ( P lt; 0. 05 or P lt; 0. 01) . Meanwhile, the levels of above cytokines were positively correlated with the level of hydroxyproline. Noteworthy, PDTC treatment led to significant decreases of above cytokines compared with the paraquat group in corresponding time points ( P lt;0. 05 or P lt;0. 01) .Conclusions Over expressions of IGF-1, TGF-β1 , PDGF, IGF-1 and CTGF may play important roles in lung fibrosis of paraquat poisoned rats. PDTC, as a b NF-κB inhibitor, may inhibits NF-κB activity and further significantly decreases expressions of cytokines, leading to significantly attenuated pulmonary inflammation and fibrosis. However, the mechanisms of PDTC intervention still remain to be explored.
ObjectiveTo explore the differential diagnosis value of subpleural bandlike ground-glass opacity (GGO) in thoracic CT in paraquat poisoning pneumonia. MethodsA retrospective study was carried out by retrieving the patients CT database from March 2013 to March 2015. The patients with paraquat poisoning pneumonia, interstitial pneumonia and pulmonary alveolar proteinosis (PAP) were recruited and their radiological characteristics of thoracic CT were analyzed. ResultsA total of 698 newly diagnosed interstitial pneumonia patients were finally enrolled in this study, 392 of them (56.2%) presented with GGO in thoracic CT. A total of 38 newly diagnosed PAP patients and 14 paraquat poisoning patients were enrolled, and GGO presented in thoracic CT of 100.0% and 42.9% of them respectively. Subpleural bandlike GGO was mostly commonly found in 83.3% of the paraquat poisoning pneumonia patients with GGO in thoracic CT, followed by 18.4% of the PAP patiens and 5.6% of the interstitial pneumonia patients with GGO in thoracic CT, which were significantly lower than that in the paraquat poisoning pneumonia patients (P < 05). GGO associated crazy paving pattern in thoracic CT was mostly commonly found in 94.7% of the PAP patients, followed by 0.5% of the interstitial pneumonia patients and none of the paraquat poisoning pneumonia patients. All the PAP patients with subpleural bandlike GGO were found associated with crazy paving pattern, while none of such association was found in the interstitial pneumonia or the paraquat poisoning pnuemonia patients. GGO coexisting with honeycombing and subpleural line were respectively found in 22.7% and 11.2% of the interstitial pneumonia patients, and none of such association was found in the PAP or the paraquat poisoning pneumonia patients. ConclusionsSubpleural bandlike GGO is mostly commonly found in paraquat poisoning pneumonia patients and rarely in PAP and interstitial pneumonia patients. Combined with crazy paving pattern and subpleural line, subpleural bandlike GGO may be a valuable feature in the diagnosis of paraquat poisoning pneumonia patients.
Objective To investigate the effects and mechanisms of hydroxychloroquine sulfate (HCQ) on pulmonary fibrosis through the PI3K/AKt/mTOR signalling pathway. Methods Paraquat intraperitoneal injection was used to establish a mouse model of pulmonary fibrosis. Thirty-six SPF C57BL/6J female mice were randomly divided into a blank group, a paraquat group (20 mg/kg) and a HCQ intervention group. The HCQ intervention group was divided into two subgroups (10 mg/kg and 30 mg/kg) according to different doses. The general condition and body weight changes of mice were observed. twenty-one days later, lung tissues were stained with hematoxylin-eosin and Masson’s pathological staining, and the content of inflammatory factors (IL-1β, IL-6, TNF-α) and hydroxyproline (HYP) were detected by ELISA. Alpha-smooth muscle actin (α-SMA), E-cadherin (E-cad), the expression levels of PI3K/Akt/mTOR pathway-related proteins, phosphatidylinositol 3 kinase (PI3K) and protein kinase B (AKt), and mammalian target of rapamycin (mTOR) were detected by Western blot. The gene expression levels of α-SMA and E-cad were detected by q-PCR. Results Compared with the blank group, the mice in the paraquat group had lower body weight, worse general condition, higher serum levels of inflammatory factors, increased lung structure destruction and collagen deposition, significantly increased HYP content, and higher expression level of PI3K/AKt/mTOR signaling pathway related proteins (all P<0.05). The expression levels of E-cad protein and gene decreased, α-SMA protein and gene increased (all P<0.05). While the HCQ intervention group improved the degree of pulmonary fibrosis in different degrees, and the relevant indexes of PI3K/AKt/mTOR signaling pathway decreased compared with the paraquat group (all P<0.05). Conclusion HCQ can ameliorate paraquat-induced pulmonary fibrosis by inhibiting the PI3K/AKt/mTOR signaling pathway.
目的:探討貫葉連翹提取物對百草枯誘導的大鼠肺纖維化模型的干預作用及機制。方法:20只Sprague-dawly大鼠隨機等分為4組:百草枯組,貫葉連翹提取物組,百草枯+貫葉連翹提取物組和對照組。百草枯液按80mg/kg一次性灌胃，貫葉連翹提取物按400mg/kg灌胃，連用3d,對照組僅用生理鹽水。于21d處死后取肺臟行HE染色鑒定,并用堿水解法測羥脯氨酸含量,同時以八木國夫熒光法測定肺組織脂質過氧化產物,鹽酸羥胺法測定組織總超氧化物歧化酶的酶活力。結果:百草枯染毒動物可致肺纖維化,羥脯氨酸和丙二醛含量明顯增高。百草枯+貫葉連翹提取物組與百草枯組比較,第21天時肺纖維化減輕,羥脯氨酸和丙二醛含量減少(Plt;0.05),與對照組相比總超氧化物歧化酶無明顯變化(Pgt;0.05)。結論:貫葉連翹提取物對百草枯誘導的大鼠肺纖維化模型有抑制作用,其機制可能與抑制脂質過氧化有關。
【摘要】 目的 探討口服百草枯中毒患者口腔護理的方法及早期護理的臨床意義。 方法 2009年1月-2010年3月，采用半隨機方法將62例白草枯中毒患者按中毒時間的長短分A組（中毒時間lt;3 d，n=32）、B組（中毒時間gt;3 d，n=3），比較兩組患者口腔潰瘍的治愈率、并發癥發生狀況，分析早期口腔護理的必要性。 結果 A組患者百草枯所致的口腔黏膜損害明顯減輕，并發癥發生率降低，為改善預后提供了條件，顯示了早期加強口腔護理的成效。 結論 重視百草枯早期口腔護理，能夠減輕口腔糜爛潰瘍痛苦，減少并發癥，提高患者生活質量。【Abstract】 Objective To investigate the clinical significance of early oral care for paraquat-poisoned patients. Methods A quasi-randomized controlled trial was used. A total of 62 paraquat-poisoned patients (from January 2009 to March 2010) were divided into experimental group and control group in order to compare the healing rate of oral ulcer, complications and the necessity of early oral care between the two groups. Results The oral mucosa lesions in experimental group obviously alleviated and the complications decreased. The effective early oral care provided the very favorable conditions for better prognosis. Conclusion The early oral care for paraquat-poisoned patients could relieve the pain of oral ulcer, reduce the complications and improve patient′s life quality.
ObjectiveTo investigate the changes of inflammatory cytokines in bronchoalveolar lavage fluid (BALF) in rats exposed to paraquat (PQ). MethodsAdult healthy SD rats were randomly divided into a control group (n=8) and three experimental groups (PQ in low dosage of 15 mg/kg,medium dosage of 30 mg/kg,and high dosage of 60 mg/kg,n=24 in each group). The rats in three experimental groups were intragastrically administered with PQ,and the rats in the control group were treated with saline by gavage. Two rats in the control group and six rats in three experimental groups were sacrificed on 1st,7th,14th,and 21st day after exposure respectively. BALF was collected for measurement of interleukin-1(IL-1),IL-6,macrophage inflammatory protein-2(MIP-2),monocyte chemoattractant protein-1(MCP-1),and biopterin by ELISA. ResultsThe levels of cytokines in all experimental groups were higher than those in the control group at any time point. In the exposure day 1 to day 14, IL-1 and biopterin levels in BALF increased significantly with the increase in PQ dose. On 14th and 21st day,IL-6 level in BALF increased significantly with the increase in PQ dosage. The levels of IL-1,IL-6,and biopterin in the experimental groups reached the peak on 14th day. On 14th day,the MIP-2 level in BALF of high-dosage group was significantly higher than that of low-dosage and medium-dosage groups (all P<0.05). The level of MCP-1 in the low-dosage group was lower than that in the medium-dosage and high-dosage groups at any time point (P<0.05). ConclusionIL-1,IL-6,MIP-2,MCP-1,and biopterin may play important roles in the development and progression of PQ-induce lung inflammation.