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BACKGROUND:During the process of acute brain injury after stroke, matrix metaloproteinase can undermine the integrity of vascular basement membrane, promote the migration of neutrophils and inflammatory factors, and cause secondary brain injury. OBJECTIVE:To investigate the activation of matrix metaloproteinase 2/9 and the degradation rule of claudin in rat models of middle cerebral artery ischemia at different ischemic durations. METHODS:Thirty-nine male SD rats were randomly divided into three groups according to different ischemic durations (3, 5 and 7 hours) . Middle cerebral artery occlusion (stroke) model was established using modified suture method,i.e., separation of the external carotid artery, inserting the suture into the internal carotid artery through the external carotid artery, and eventualy reaching the middle cerebral artery. The ischemic duration in these three groups was respectively 3 , 5 and 7 hours. After 2 hours of reperfusion, Zea-Longa score and Ludmila Belayev score, brain infarct area, matrix metaloproteinase 2/9 activities and claudin 5 degradation were determined in each group. RESULTS AND CONCLUSION:With the extension of ischemic duration, brain infarct area gradualy increased, central nervous system damage gradualy aggravated, matrix metaloproteinase 2/9 activities gradualy increased, and claudin-5 expression gradualy decreased. There were significant differences between any two ischemic durations in terms of each of above-mentioned indices. The results indicate that after long duration of ischemia, the progressive damage of brain tissue can cause the gradual increase of activation of matrix metaloproteinase 2/9 and the gradual degradation of claudin 5.
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Objective To study the effect of repeated rectal exposure of low -dose simian immunodeficiency virus on the systemic cellular immunity in monkeys .Methods Eight 3-to 4-year old rhesus macaques ( Macaca mulatta) (male:female 1:1) were used in this study.The monkeys were inoculated with 10 TCID50 SIVmac239 virus through rectum twice a week for consecutive 6 weeks to establish a multiple rectal exposure model of SIVmac 239 virus infection.Then, plasma viral load, CD4+ T cell count, T cell subsets and IFN-γsecretion of the experiment monkeys were determined . Results Low-dose SIVmac239 virus induced some changes in the immune system through the rectal mucosa , but didn’t induce typical infection.Repeated rectal mucosal low-dose virus exposure can activate the cellular immune system . Conclusions This study defines the effect of repeated low -dose simian immunodeficiency virus exposure on the systemic cellular immunity, and provided basic information for HIV-1 vaccine research.
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Objective To compare the differences of lung pathological changes of acute lung injury in mice in-duced by lipopolysaccharide ( LPS) and graphite particles, and to explore the possible mechanisms of acute lung injury in-duced by fine particles of different origins.Methods 140 male specific-pathogen-free Kunming mice weighing 18-20 g were randomly divided into 7 experimental groups, in addition to the normal control group.The experimental groups were treated by intratracheal instillation of LPS solution or graphite powder suspension in different doses, respectively, to induce acute lung injury in the mice.The mortality of the mice was observed, and pathological changes of the lung tissues were ex-amined by light and transmission electron microscopy.Western blot was used to detect the protein expression of neutrophil elastase ( NE) in lung tissues , and real-time quantitative PCR was used to detect mRNA expression of monocyte chemotac-tic protein-1 ( MCP-1) in the lung tissue .Results Compared with the normal control group, some pathological changes were observed in the lung tissues of the groups L ( LPS) and G ( graphite) .There were numerous macrophages in the lung tissues in the group G mice, and exudate, mainly neutrophils, in the lung tissues of the group L.The NE protein expres-sion in the lung tissue was significantly higher than that of the normal control group ( P<0.05) , and there was also a sig-nificant difference between the groups L and G (P<0.05).The MCP-1 mRNA expression in lung tissues was higher in the control group (P<0.01), and there was also a significant difference between the groups L and G (P<0.01).Conclu-sions Diverse types of particulate matters induce different pathological changes in the lungs, therefore the mechanism may also be different in the inflammatory responses.It means that the lung injuries caused by fine particles of mixed composition may have complex mechanisms.
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Objective To understand the dynamic rules of schistosomiasis endemic situation before and after reaching the criteria of schistosomiasis transmission controlled or transmission interrupted,so as to provide the evidence for improving schis-tosomiasis control. Methods Wuling District,Xihu District and Linli County were selected and investigated retrospectively to collect the schistosomiasis epidemiological information 10 years before they reached the criteria of transmission controlled and the subsequent years until 2008. A database of retrospective investigation was established for analyzing the trends and rules of changes of the Oncomelania hupensis snail status and infection status of cattle and human. Results In Wuling District,the en-demic situation was declining,and no schistosome infection persons,animals and snails were found after 1974. There was no re-bound until 2008. In Xihu District,the endemic situation reached the criteria of transmission controlled in 1997,and the endem-ic situation was stable. The human infection rate was positively correlated with the area of infection snails(r=0.584,P<0.05). In Linli County,there were no snails,no infected persons and cattle twice,but 2 endemic rebounds,and there were positive corre-lations between the densities of living snails and the infection rates of human and animal during the endemic rebound period. Conclusion The snail status is an important indicator of schistosomiasis endemic rebound. Therefore,the snail control is one of the most important schistosomiasis control measures.
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AIM: To observe the effects of sera containing Kang xian ling (a traditional Chinese medicine) on c-Met and its downstream MAPK signal molecules in HK-2 cells treated with transforming growth factor-β_1(TGF-β_1), so as to further explore the effective mechanism of anti-renal fibrosis of the traditional Chinese medicine. METHODS: Rat sera containing herbs were collected after rats were intragastrically administered with the herbs. HK-2 cells activated by TGF-β_1 were incubated with different heat-inactivated sera. The proliferation and expression of MAPK and the phosphorylation of MAPK in HK-2 cells were detected by Alarm blue and immunoblotting. RESULTS: No significant difference of cell proliferation between any two groups was observed. C-Met and the phosphorylation of its downstream molecules were also observed after incubated with different sera. CONCLUSION: The receptor c-Met of hepatocyte growth factor, and the phosphorylation of its downstream MAPK molecules can be regulated by the sera containing Kang xian ling.
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OBJECTIVE: To study the effect of Kangxianling Decoction (KXLD), a compound traditional Chinese herbal medicine, on expression of hepatocyte growth factor (HGF) mRNA and phosphorylations of extracellular signal-regulated protein kinase 1/2 (ERK 1/2) and p38 in renal tissue of rats with unilateral ureteral obstruction (UUO). METHODS: Eighteen male SD rats were randomly divided into 3 groups: sham-operated group, untreated group and KXLD-treated group. A rat model of renal interstitial fibrosis was established by UUO. Rats with UUO were sacrificed after intragastric administration of KXLD for 14 days, and the parameters such as serum creatinine (SCr), blood urea nitrogen (BUN) and hydroxyproline in the kidney of rats in 3 groups were analyzed. The expression of HGF mRNA in kidney tissue was determined by reverse transcription polymerase chain reaction. The expressions of c-Met protein, ERK1/2 protein, p38 protein and the phosphorylations of ERK1/2 and p38 were determined by Western blotting method. RESULTS: The levels of SCr, BUN and hydroxyproline in the untreated group were significantly increased as compared with those in the sham-operated group (P<0.05). The expression of HGF mRNA in the untreated group was significantly down-regulated. The expression of c-Met protein and the phosphorylations of ERK1/2 and p38 in the kidney tissue of rats with UUO in the untreated group were significantly up-regulated. After intervention with KXLD, the phosphorylations of ERK1/2 and p38 were all significantly inhibited except for c-Met expression. The HGF mRNA was increased in KXLD-treated group. CONCLUSION: KXLD can decrease the level of collagen in the obstructed kidney of rats with UUO and alleviate the renal interstitial fibrosis in rats with UUO through enhancing the HGF mRNA expression and inhibiting the phosphorylations of ERK1/2 and p38.
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AIM: To study the effect of Kang Xianling decoction,comprised of dahuang,danshen,taoren,niuxi and danggui,on TGF-?1-Smad pathway in unilateral ureteral obstruction rat model.METHODS: Eighteen male SD rats were divided into 3 groups,sham group,model group and model group treated with Kang Xianling decoction randomly.Renal interstitial fibrosis model was established in rats by unilateral ureteral obstruction(UUO).After treatment for additional 14 d,parameters of hydroxyproline in obstructed kidney from 3 groups were analyzed.Rats were sacrificed and the pathological statuses of their kidneys were checked by HE staining and electron microscopy.Transforming growth factor-?1(TGF-?1) mRNA in kidney tissue was determined by RT-PCR.TGF-?1 receptor Ⅰ(T?RⅠ),TGF-?1 receptorⅡ(T?RⅡ),phosphorylated Smad2 and Smad2 protein were determined by Western blotting.RESULTS: Parameters of hydroxyproline in animals of model group were significantly increased than those in sham operation group(P