AIMTo study the effect of ischemic preconditioning on lung injury following ischemia/reperfusion (I/R) in the hind limbs of rats.

METHODSWistar rats were randomly divided into four groups (n=8): control group,limbs ischemia/reperfusion (LI/R) group, ischemia preconditioning (IPC) group and L-NAME group. At the end of the experiment, blood/gas analysis and the contents of serum MDA, NO, ET and lung tissue MDA, NO, ET, MPO were measured. Meanwhile, lung index and W/D) of lung were measured.

RESULTSAfter the rats' hind limbs suffered ischemia/reperfusion, the level of PaO2 decreased and the values of W/D, LI, MPO of the lung issure and MDA, NO, ET of plasma and lung all increased significantly in the LI/R group; but the ratio of NO/ET decreased. Compared with LI/R group, the contents of NO and ratio of NO/ET increased but other parameters decreased in the IPC group. Compared with IPC group, the contents of NO and ratio of NO/ET decreased, but other parameters increased in the L-NAME group.

CONCLUSIONThe IPC can attenuate lung injury following IR in the hind limbs of rats, which may correlated with the increase of NO.

Acute Lung Injury ; prevention & control ; Animals ; Extremities ; blood supply ; Ischemia ; physiopathology ; Ischemic Preconditioning ; methods ; Lung ; blood supply ; Male ; Random Allocation ; Rats ; Rats, Wistar ; Reperfusion Injury ; metabolism ; prevention & control

Animals ; Hindlimb ; blood supply ; Ischemic Preconditioning ; Lung ; metabolism ; Male ; P-Selectin ; metabolism ; Rats ; Rats, Wistar ; Reperfusion Injury ; metabolism

AIMTo explore the effect of ligustrazine injection on the expression of heme oxygenase-1 (HO-1) in rabbits with pulmonary ischemia/reperfusion injury after.

METHODSSingle lung ischemia/reperfusion injury animal model was used in vivo. Twenty rabbits were randomly divided into two groups( n = 10, in each), pulmonary ischemia/reperfusion injury (I/R) group and I/R + ligustrazine injection (LGT) group. The tissue slides were stained by immunohistochemistry (IHC) and in situ hybridization (ISH) for HO-1 to detect the expression of HO-1 in lung and to analyze the absorbance, wet to dry ratio of lung tissue weight (W/D) and the injured alveoli rate (IAR) were measured at 180 minutes after lung reperfusion. Meanwhile the lung tissue slide was prepared for electron microscopic observation at 180 minutes after reperfusion.

RESULTSHO-1 expression was upregulated in two groups in the pulmonary endothelial cells, part of pulmonary vascular smooth muscle cells, extima of vessels and epithelial cells of airway, the absorbance was 0.168 +/- 0.016 (0.148 +/- 0.013), 0.186 +/- 0.014 (0.158 +/- 0.012) respectively.The LGTI group showed higher absorbance than those of the I/R group (P < 0.01), lower W/D and IAR values than those of the I/R group (P < 0.01) significantly and lighter abnormal changes of the lung tissue in morphology than those of the I/R group.

CONCLUSIONLigustrazine injection possesses notable protective effects on I/R in rabbits by increasing the expression of HO-1 in lung.

Animals ; Disease Models, Animal ; Heme Oxygenase-1 ; metabolism ; Lung ; blood supply ; metabolism ; Pyrazines ; pharmacology ; Rabbits ; Reperfusion Injury ; metabolism

OBJECTIVEErythropoietin and erythropoietin receptor (EPO-R) are expressed in many kinds of tumors. The EPO/EPO-R signaling is involved in tumor cell proliferation, invasion and angiogenesis. The aim of this study was to detect the expression of EPO-R in non-small cell lung cancer (NSCLC), and explore its correlation with angiogenesis.

METHODSThe expression patterns of EPO and EPO-R in 31 cases of NSCLC tissues were detected by immunohistochemistry, and that in benign lung lesions of 21 patients as control. To analyze the correlation of EPO/EPO-R expression patterns and clinicopathological factors. CD34 was used to label the vascular endothelial cells and calculate the microvessel density (MVD).

RESULTSThe positive rates of EPO and EPO-R expression in NSCLC were 67.7% and 96.8%, respectively, significantly higher than those in the control ones. The positive rates of EPO and EPO-R expression in adjacent tissues were 19.4% and 35.5%, and in benign lesions were 9.5% and 19.0%, respectively (P < 0.001). The expression patterns of EPO/EPO-R were not related with pTNM stage, histological type, histological grade and lymph node metastasis (P > 0.05). Increased MVD was correlated with poor differentiation, lymph node metastasis, and advanced stage.

CONCLUSIONSHigh expression of EPO/EPO-R in NSCLC patients suggest that they may be involved in tumorigenesis. EPO/EPO-R expression and MVD are closely related, and they might be an endogenous stimulant of angiogenesis during the progression of non-small cell lung cancer. It may provide evidence for clinical diagnosis.

Antigens, CD34 ; metabolism ; Carcinoma, Non-Small-Cell Lung ; blood supply ; metabolism ; pathology ; Erythropoietin ; metabolism ; Humans ; Lung Neoplasms ; blood supply ; metabolism ; pathology ; Lymphatic Metastasis ; Microvessels ; pathology ; Neoplasm Staging ; Neovascularization, Pathologic ; Receptors, Erythropoietin ; metabolism

OBJECTIVE: To detect the expressions of chemokines interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-1 (MIP-1) mRNA in non-small cell lung cancer (NSCLC) tissues, to analyze their relationship with microvessel counts (MVC), and their significance in clinic pathologic features of NSCLC. METHODS: In situ hybridization was used to measure the expressions of chemokine IL-8, MCP-1, and MIP-1 mRNA in 40 NSCLC tissues and 10 normal pulmonary tissues, and immunohistochemical staining was carried out to measure the MVC in the above tissues. RESULTS: The positive ratios of IL-8, MCP-1, and MIP-1 mRNA in the 40 NSCLC tissues were apparently higher than those in the 10 normal contrast tissues and the difference was statistically significant. The numbers varied accordingly with the different clinic pathologic features of NSCLC, showing that Group T(3) > Group T(2) or Group T(1), Group III stage> Group II stage> Group I stage Group lymph node and remote transferred > Group non-transferred, and Group of survival time no more than 3 years > Group of survival time more than 3 years. The positive expressions among IL-8, MCP-1,and MIP-1 mRNA and between these and the MVC all had mutually positive correlation. CONCLUSION Chemokine IL-8, MIP-1, and MIP-1 in NSCLC tissues might cooperate with one another to promote the tumor angiogenesis and affect the progression, metastasis and prognosis of the tumor.
Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; blood supply ; metabolism ; Chemokine CCL2 ; metabolism ; Female ; Humans ; Interleukin-8 ; metabolism ; Lung Neoplasms ; blood supply ; metabolism ; Macrophage Inflammatory Proteins ; metabolism ; Male ; Middle Aged ; Neovascularization, Pathologic ; Prognosis

AIMTo investigate the effect of ligustrazine (LGT) on expression of Fas/FasL mRNA during pulmonary ischemia/reperfusion injury (PI/RI) in the rabbits.

METHODSSingle lung ischemia/reperfusion animal model was used in this study. The rabbits were randomly divided into three groups (n = 30, in each): sham operated group (Sham), I/R group (I/R) and I/R + LGT group (I/R + LGT). Changes of several parameters which included apoptotic index (AI), wet to dry ratio of lung tissue weight (W/D) and index of quantitative assessment of histologic lung injury (IQA) were measured at 1h, 3h, 5h after reperfusion in lung tissue. Meanwhile the location and expression of Fas/FasL mRNA were observed. Lung tissue was prepared for light microscopic and electron microscopic ob servation at 1 h, 3 h, 5 h after reperfusion.

RESULTSAs compared with group I/R, Fas/FasL mRNA slightly expressed in intima and extima of small pulmonary artery, alveoli, and bronchiole epithelia in group LGT. The values of AI, W/D and IQA showed significantly lower in group I/R + LGT than that in group I/R at 1 h, 3 h, 5 h after reperfusion in lung tissue (P < 0.01 and P < 0.05). Meanwhile, abnormal changes of the lung tissue in morphologically were lessen markedly in group I/R + LGT.

CONCLUSIONLigustrazine has notable protective effects on PI/RI in rabbits by inhibiting Fas/FasL mRNA express in lung tissue and decreasing apoptosis.

Animals ; Apoptosis ; Fas Ligand Protein ; metabolism ; Lung ; blood supply ; Lung Injury ; metabolism ; pathology ; Pyrazines ; pharmacology ; RNA, Messenger ; genetics ; Rabbits ; Reperfusion Injury ; metabolism ; pathology ; fas Receptor ; metabolism

Humans ; Lung Neoplasms ; blood supply ; pathology ; Lymphatic Vessels ; pathology ; Neovascularization, Pathologic ; metabolism ; Vascular Endothelial Growth Factors ; chemistry ; metabolism ; physiology

OBJECTIVE: To observe the effect of intrauterine hypoxia on the development of rat lung after birth under ordinary pressure and normoxia, on the expression of vascular endothelial growth factor (VEGF) in the lung as the age increasing after birth, and to provide experimental basis for the treatment of intrauterine hypoxia after baby was born. METHODS: Intrauterine hypoxia models were established. The rats were divided into an air-control group (the control group) and a hypoxic 6-day group (the hypoxic group). All rats were fed under normal pressure and normoxia after they were born. At postnatal 7, 14, and 21 days, we measured the pulmonary vascular morphometry, detected the expression of VEGF protein with immunohistochemisty, the expression of VEGF mRNA with real-time PCR, and observed the alteration of capillary endothelium in the lung tissues under the electron microscope. RESULTS: The expression of VEGF protein and VEGF mRNA in the 2 groups increased as the rats grew, but the expression increased slower in the hypoxic group than that in the control group. The increase curve of the 2 groups crossed. There was no significant difference between the 2 groups in the pulmonary vascular morphometry at each experiment time point. Hyperplasia of capillary endothelium decreased with age. Cellular edema of capillary endothelium was obvious especially at the 14th day after birth under the electron microscope. CONCLUSION The expression of VEGF protein and VEGF mRNA has slower increase in the intrauterine hypoxic rats than that in the normal control rats. The expression of VEGF may influence the development of lung vessel after rats was born.
Animals ; Animals, Newborn ; Endothelium, Vascular ; pathology ; Hypoxia ; Lung ; blood supply ; metabolism ; RNA, Messenger ; Rats ; Vascular Endothelial Growth Factor A ; metabolism

AIMTo explore the possible impact of endogenous hydrogen sulfide (H2S) on the content and metabolism of collagen in rats with high pulmonary blood flow.

METHODSThirty-two male SD rats, weighing 120-140 g, were randomly divided into 4 groups (n = 8), shunt group, shunt + PPG (propargylglycine, an antagonist of endogenous H2S producing enzyme) group, sham group and sham + PPG group. Rats in shunt group and shunt + PPG group were subjected to an abdominal aorta-inferior vena cava shunt to create an animal model of high pulmonary flow. In the sham group and sham + PPG group, rats experienced the same experimental processes except the shunting procedure. After 4 weeks of experiment, lung tissue H2S content of rat was determined by a modified sulfide electrode method. Pulmonary artery collagen I, collagen III, MMP-13 and TIMP-1 protein expressions of rat were investigated by immunohistochemistry.

RESULTSAfter 4 weeks of experiment, lung tissue H2S content increased significantly in rats of shunt group as compared with that of sham group (P < 0.05). Pulmonary artery collagen I and collagen III protein expression increased obviously in rats of shunt group as compared with that of sham group (P < 0.01). After administration of PPG for 4 weeks, lung tissue H2S content decreased significantly in rats of shunt + PPG group as compared with that of shunt group (P < 0.05). In contrast to rats in shunt group, collagen I and collagen III protein expression in pulmonary arteries of shunt + PPG group increased significantly, respectively (P < 0.05). Compared with rats of shunt group, pulmonary artery MMP-13, TIMP-1 and the ratio of MMP-13/TIMP-1 in shunt + PPG group down-regulated significantly (P < 0.05).

CONCLUSIONEndogenous H2S might play a protective regulatory role in the development of pulmonary hypertension and pulmonary vascular structural remodelling in rats by decreasing the content of pulmonary artery collagen resulting from catabolism of collagen.

Animals ; Collagen ; metabolism ; Hydrogen Sulfide ; metabolism ; Lung ; blood supply ; metabolism ; Male ; Matrix Metalloproteinase 13 ; metabolism ; Pulmonary Artery ; metabolism ; Rats ; Rats, Sprague-Dawley ; Tissue Inhibitor of Metalloproteinase-1 ; metabolism

Maspin belongs to the serine protease inhibitor (serpin) family and has been proven to be a suppressor of tumor growth and metastasis in many types of tumors. The purpose of this study was to investigate the expression of maspin in non-small cell lung cancer (NSCLC) and its relationship to vasculogenic mimicry (VM). A total of 160 specimens of NSCLC were involved in this study and 20 specimens of normal lung tissue served as controls. VM, microvessel density (MVD) and the expression of maspin were detected by using immunohistochemical staining. The results showed that the positive rates of maspin and VM in the NSCLC group were 48.1% (77/160) and 36.9% (59/160), respectively, which were significantly different from those in the control group with the positive rates of maspin and VM being 100% and 0% respectively (P<0.05). VM, MVD and the expression level of maspin were significantly related to tumor differentiation, lymph node metastasis, clinical stages and postoperative survival time (all P<0.05). The maspin expression in patients with squamous cell carcinoma was significantly higher than that in those with adenocarcinoma (P<0.05). The maspin expression was negatively correlated with VM and MVD, and there was a positive correlation between VM and MVD. Maspin-negative expression, VM and high MVD score were negatively related to the 5-year-survival rate. PTNM stages, VM, MVD and maspin expression were independent prognostic factors for NSCLC (P<0.05). It was suggested that the loss of expression of maspin may participate in the invasion and metastasis of NSCLC and it has a positive relationship to VM in NSCLC. Combined detection of maspin, VM and MVD may help predict the progression and prognosis of NSCLC.
Adult ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung ; blood supply ; metabolism ; pathology ; Female ; Humans ; Lung Neoplasms ; blood supply ; metabolism ; pathology ; Male ; Microvessels ; pathology ; Middle Aged ; Neovascularization, Pathologic ; pathology ; Serpins ; metabolism ; Tumor Cells, Cultured ; Young Adult