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Objective To investigate the possible mechanism of Xuebijing injection in regulating abnormal degradation of pulmonary vascular endothelial calyx to improve acute lung injury induced by severe heatstroke.Methods Forty-eight Wistar rats were randomly divided into control group,heatstroke group and Xuebijing group.Before heatstroke induction,rats in Xuebijing group were administrated with Xuebijing injection(2 ml/kg,2 times/d)for 3 days.All rats were exposed to an environment with temperature of(40±2)℃and humidity of 65%±5%for 60 minutes to induce heatstroke.Two hours later,the lung wet/dry weight ratio was recorded;the concentration of proteins in BALF was measured;the pulmonary vascular permeability was measured by Evans blue(EB);HE staining was used to observe the pathological changes of lung tissue;the changes of hyaluronic acid(HA)on the surface of pulmonary vessels were observed by immunofluorescence;Western blotting was used to detect the expression of Syndecan-1,Glypican-1,VE-Cadherin,Occludin,VCAM-1 and E-selectin in lung tissues;Enzyme-linked immunosorbent assay(ELISA)was utilized to quantify the concentration of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)in serum and heparanase(HPA)in lung tissue.Results Xuebijing could decrease the lung wet/dry weight ratio,reduce protein exudation and improve pulmonary vascular permeability(P<0.01);reduce the histological injury(P<0.01);reduce the degradation of HA,Syndecan-1 and Glypican-1 on the surface of pulmonary vessels(P<0.01);increase the expression of VE-Cadherin and Occludin(P<0.01);regulate the overexpression of VCAM-1 and E-selectin(P<0.01);down-regulate the expression of TNF-α,IL-6 and HPA(P<0.01).Conclusion Xuebijing injection decrease the expression of HPA,improve the disintegration of pulmonary vascular endothelial calyx,repair the integrity of pulmonary vessels,reduce the damage of cell connections,down-regulate the expression of adhesion molecules,inhibit the inflammatory reaction,relieving acute lung injury caused by severe heat stroke.
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Objective To explore the pattern of early expression and secretion of tissue factor(TF)in vascular endothelial cells induced by heat stress.Methods Thirty SPF-rated C57BL/6 male mice were randomly divided into five groups:the control group and groups of indicated recovery time,including 0,3,6,and 9 h in room temperature after heat stress(n=6).Mice in the heat stress groups were exposed to an animal incubator to reach 42.5℃for core body temperature for heat stroke.We analyzed the histopathological changes in the liver,lung,and kidney tissues with HE staining.We measured the TF mRNA in mice tissues by RT-qPCR and the plasma concentration of TF in mice with a commercial ELISA kit.Human umbilical vein endothelial cells(HUVECs)were placed in a culture incubator to build an in vitro heat stress model.HUVECs were divided into five groups,including a control group and groups of indicated recovery time,including 0,3,6,and 9 h after heat stress.We quantified the expression of TF mRNA and protein in HUVEC cells by RT-qPCR,Western blotting,and immunofluorescence and measured the secreted TF with a commercial ELISA kit.Results No significant pathological injury was observed in the tissues of the control group.Mice treated with heat stress had various degrees of structural injuries and hemorrhagic and inflammatory changes in multiple tissues.Compared to control group,the expression of TF mRNA significantly increased in the kidney of heat stress-treated mice with 0 and 3 h recovery time(1.719±0.018,1.241±0.178 vs.1.000±0.063),the lung with 3 h recovery time(2.444±0.511 vs.1.000±0.106)and the liver with 6 h recovery time(7.312±0.618 vs.1.000±0.147)(P<0.05).The concentration of TF in plasma also sustainedly elevated in mice with 0,3,6,and 9 h recovery time after heat stress as compared to control group[(132.426±17.920)pg/ml,(119.400±10.267)pg/ml,(107.374±13.495)pg/ml,(163.767±22.810)pg/ml vs.(75.479±13.831)pg/ml,respectively,P<0.01].The expression levels of TF mRNA were higher in heat stress HUVECs with 6 h and 9 h recovery time than the control cells(1.905±0.354,2.564±0.297 vs.1.000±0.097,P<0.01).Secreted TF in the supernatant from HUVECs treated with heat stress and different recovery time also increased significantly[(36.309±4.101)pg/ml,(38.425±5.484)pg/ml,(41.655±4.380)pg/ml,(43.586±4.718)pg/ml vs.(14.996±0.254)pg/ml,P<0.01].Conclusion Heat stress increased early expression and secretion of TF in vascular endothelial cells.Vascular endothelial cells may be a main source of circulating TF in heat stroke.
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Objective To explore the effect ofdexmedetomidine on the lipopolysaccharide (LPS) stimulated PC12 cells and its potential mechanism.Methods PC12 cells were treated by LPS with a concentration of 400μg/ml.The cell viability,the concentrations ofinterleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) in the cell culture supernatant were measured after 3-,6-,or 12-h treatment.The expressions of toll-like receptor 4 (TLR4),myeloid differentiation factor 88 (MyD88) and phosphorylated p65 (p-p65) were measured.In the second part,PC12 cells were cultured under four different treatments,that is,normal culture media in first group,400μg/ml LPS in second group,100μmol/L dexmedetomidine in third group,400μg/ml LPS and100μmol/L dexmedetomidine in fourth group.The indexes mentioned above were measured 6 hours after LPS and DEX treatments.Results The cell viability was decreased after LPS treatment,and the concentrations of IL-6 and TNF-α were increased significantly.Compared with control group,the concentrations in 3-,6-,12-h groups showed statistically significant differences (P＜0.05),especially after 6 hours.The TLR4/MyD88/NF-κB pathway was activated after LPS stimuli and reached the peak value.Compared with LPS treatment group,PC 12 cell apoptosis rate,the concentrations of IL-6 and TNF-α and the expressions of TLR4,MyD88 and p-p65 were decreased.The differences between LPS+DEX group and LPS group was statistically significant (P＜0.05).Conclusion Dexmedetomidine has a protective effect on LPS stimulated PC 12 cells via the inhibition of inflammatory response.
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Objective To investigate the influences of mesenteric lymph duct ligation (LDL) on the coagulation function in rats with severe heat stroke (SHS). Methods Forty male Wistar rats were randomly and equally divided into control, heat stroke sham (HSS), HSS-LDL, severe heat stroke (SHS) and SHS+LDL groups. Mesenteric lymph ducts were ligated in HSC-LDL and SHS-LDL groups before reproduction of SHS model. SHS rat models were reproduced in a prewarmed incubator. Peripheral blood was drawn to determine the parameters pertaining to blood coagulability including prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimmer and platelet count (PLT), and lung and kidney histopathology was observed after heat stroke. Results Compared with those in control group, no obvious changes were observed in the coagulation indices in HSS and HSS-LDL group. While PT and APTT significantly prolonged, PLT remarkably decreased, D-dimmer markedly increased in SHS group (P<0.05). The coagulation indices presented a recovery trend to certain extent in SHS-LDL group. Histopathological examination of the kidney and lung showed severe hemorrhagic and congestive lesions in SHS group. Mesenteric lymph duct ligation alleviated the coagulation disorders and histopathological lesions. Conclusion The entrance of toxic agents through lymphatic passage may be the pathogenetic factor in producing coagulopathy, and ligation of the mesenteric lymph ducts might prevent the entrance of toxic materials and alleviate the injury to the blood coagulation property and internal organs.
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Objective To observe the dynamic changes in mesenteric lymph microcirculation and its kinetics in rats suffering from severe heatstroke (SHS), and to explore the role of mesenteric lymph in the pathogenesis of SHS. Methods SHS rat models were reproduced in an incubator with high temperature and high humidity. The vital signs and the time of onset of SHS in rats were recorded continuously during the process of heat stress. Parameters of mesenteric lymph microcirculation including Index-I, Index-II, L.D-Index, and intra-lymphatic pressure before heat exposure, 60min after heat exposure, and onset of SHS were collected and analyzed. Mesenteric lymph was collected at 30-min interval, and its volume of production was measured dynamically. Results Rat SHS model was reproduced successfully. After exposure to the environment with high temperature and high humidity, the core temperatures of the rats raised to 42°C at the time point of 60min, and HS onset occurred at about 77min. Mesenteric lymph-vessel contraction indices including Index-I, Index-II, L.D-Index, lymph-vessel pressure and mesenteric lymph flow decreased significantly at the time point of 60min (P<0.05). However, all the above parameters increased at the time point of SHS onset (P<0.05), but had not yet reached the normal levels before hyperthermia and high humidity exposure (P<0.05). Conclusion Changes of mesenteric lymph microcirculation in rats with SHS shows a dynamical regularity, which may take part in the pathogenesis of SHS.
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Objective To explore the effect of mesenteric lymph from rats suffering from heat stroke (SHS) on the inflammatory activity of vascular endothelial cells. Methods Rats were placed in a prewarmed incubator to reproduce heat stroke. Human umbilical vein endothelial cells (HUVECs ECV-340) were incubated in 5% mesenteric lymph collected pre-, during-, and post-HS for 3 and 6 h respectively in vitro. The levels of high mobility group protein B1 (HMGB1), tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and IL-6 of ECV-340 cells were determined. The expression of intercellular adhesion molecule 1 (ICAM-1) mRNA and NF-κB activity of ECV-340 were also assayed. Results The levels of HMGB1, TNF-α, IL-1β and IL-6 induced by SHS mesenteric lymph of rats significantly increased after heat treatment (P<0.05), and this effect was enhanced with prolongation of exposure time (P<0.05). The expression of ICAM-1 mRNA and NF-κB activity were significantly elevated after being activated by SHS mesenteric lymph (P<0.05). Conclusion HS mesenteric lymph probably activates the inflammatory responses of vascular endothelium, which is closely associated with the pathogenesis of SHS.
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<p><b>OBJECTIVE</b>To investigate the expression and clinical implication of tissue inhibitor of metalloproteinase-1 (TIMP-1) in colorectal carcinoma.</p><p><b>METHODS</b>TIMP-1 expression in 54 colorectal carcinoma was observed by SP immunohistochemical method, and the results were analyzed in relation to the clinical data of patients.</p><p><b>RESULTS</b>TIMP-1 was localized on the membrane and in the cytoplasm of the enteric epithelial cells, and its expression rate was 100% in normal tissue but only 59.6% (31/52) in colorectal carcinoma tissues. In addition, the expression rate of TIMP-1 was higher in the tumor tissues without lymph node metastasis than in tissues with lymph node metastasis (P<0.05).</p><p><b>CONCLUSION</b>The expression of TIMP-1 is inversely correlated to lymph node metastasis of colorectal carcinoma, and decreased TIMP-1 expression may play a role in the progression of colorectal carcinoma.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Colorectal Neoplasms , Metabolism , Pathology , Epithelial Cells , Chemistry , Pathology , Immunohistochemistry , Lymphatic Metastasis , Tissue Inhibitor of Metalloproteinase-1ABSTRACT
<p><b>OBJECTIVE</b>To explore the endoscopic and histopathological morphology of large intestinal serrated adenomas (SA).</p><p><b>METHODS</b>The endoscopic and pathological data of 71 SA patients, diagnosed in the Digestive Endoscopy Center, Nanfang Hospital from January 2002 to July 2005, were analyzed retrospectively.</p><p><b>RESULTS</b>Forty-seven of the 71 serrated adenomas were protruded (sessile 23, semipedunculated 5, pedunculated 23) and 24 were superficial (flat 16, laterally spreading 8). The mean sizes of the protruded and superficial SA were 10.5 mm and 16.6 mm, respectively, and both of them were frequently located in the sigmoid and rectum. Histopathologically, SA contained tubular glands in 53, tubulovillous glands in 9 and villous glands in 9 cases. Mild dysplasia was found in 47 SAs, moderate dysplasia in 22 SAs, and canceration foci in 2 SAs. The dysplasia of SAs (<10 mm) was significantly better than that of SAs (>or= 10 mm) (P< 0.01). Most IV and III L pit SAs presented villous glands (64%) and tubular glands (68%), respectively. 40% of hyperplastic polyps-like SAs, composed of tubular glands,showed II pit pattern. Atypia in II pit SAs was similar to that in IIIL pit SAs, but was worse than that in IV pit SAs.</p><p><b>CONCLUSION</b>Polyps with II pit pattern possibly are SAs sometimes. SA with the common characters of neoplastic polyps,should be regarded as a new potential precancerous lesion.</p>