摘要
Provirus integration site Moloney murine leukemia virus (Pim-1) is a proto-oncogene reported to be associated with cell proliferation, differentiation and survival. This study was to explore the neuroprotective role of Pim-1 in a rat model subjected to optic nerve crush (ONC), and discuss its related molecules in improving the intrinsic regeneration ability of retinal ganglion cells (RGCs). Immunofluorescence staining showed that AAV2- Pim-1 infected 71% RGCs and some amacrine cells in the retina. Real-time PCR and Western blotting showed that retina infection with AAV2- Pim-1 up-regulated the Pim-1 mRNA and protein expressions compared with AAV2-GFP group. Hematoxylin-Eosin (HE) staining, γ-synuclein immunohistochemistry, Cholera toxin B (CTB) tracing and TUNEL showed that RGCs transduction with AAV2-Pim-1 prior to ONC promoted the survival of damaged RGCs and decreased cell apoptosis. RITC anterograde labeling showed that Pim-1 overexpression increased axon regeneration and promoted the recovery of visual function by pupillary light reflex and flash visual evoked potential. Western blotting showed that Pim- 1 overexpression up-regulated the expression of Stat3, p-Stat3, Akt1, p-Akt1, Akt2 and p-Akt2, as well as βIII-tubulin, GAP-43 and 4E-BP1, and downregulated the expression of SOCS1 and SOCS3, Cleaved caspase 3, Bad and Bax. These results demonstrate that Pim-1 exerted a neuroprotective effect by promoting nerve regeneration and functional recovery of RGCs. In addition, it enhanced the intrinsic regeneration capacity of RGCs after ONC by activating Stat3, Akt1 and Akt2 pathways, and inhibiting the mitochondrial apoptosis pathways. These findings suggest that Pim-1 may prove to be a potential therapeutic target for the clinical treatment of optic nerve injury.
摘要
Objective To evaluate the efficacy of serum PCT level in deciding the development and progno-sis of sepsis and its conrrelation with APACHE Ⅱ scoring.Methods 56 patients of sepsis accepted intensive care treatment and were all given APACHE Ⅱ scoring within the first 24 h after admission to ICU.The PCT level at dif-ferent time(1 d,3 d,5 d-7 d,10 d after admission)was detected.All these patients were divided into survival group and death group based on the 28-day fatality.Results The PCT level declined gradually with the treatment and it decreased obviously from the third day in comparison with the original level before admission [survival group/death group:(2.98±0.48)μg/L/(4.98±0.66)μg/L vs(4.04±0.50)μg/L/(6.02±0.50)μg/L](P<O.05).The PCT level in survival group declined quickly with the patients'condition improved and almost decreased to the normal level in the 10 day[0.48 ±0.18)μg/L],while the PCT in the death group was still in a higher level than normal even though it showed a tendency to decrease[(4.04±0.45)μg/L].The APACHE Ⅱ scores in death group was obviously higher than the survival group(death group/survival group:25.86±8.73/12.07±6.20,P<0·05).The coefficient of correlation between PCT and APACHE Ⅱ scoring was 0.656(P<0.05).Conclusion PCT,a single serology index,is characterized with conveniently and quick-which is strongly correlated with APACHE Ⅱscoring.
摘要
BACKGROUND:Hepatocyte growth factor(HGF) is a kind of multifunctional growth factor,which can accelerate cell growth,transition and genesis in various organs.In cardiovascular system,HGF has reported to have anti-apoptotic,anti-fibrotic,as well as repair endothelial cell injury effects,suppose that HGF has relationships with hypertension.OBJECTIVE:To investigate the effect of HGF on blood pressure,vascular endothelial system and renin-angiotensin system(RAS) in spontaneously hypertensive rats,further more,to discuss the mechanisms between HGF and hypertension.DESIGN,TIME AND SETTING:The randomized control experiment on animal was performed at the Department of Cardiology,First Affiliated Hospital of Anhui Medical University from March to July 2007.MATERIALS:The exogenous HGF power was purchased from America Peprotech Company.Rats with 14-weeks-old,weighting 200-250 g,were randomly divided into the experimental and spontaneous hypertension groups,WKY rats were serves as the control group,with 12 animals in each group.METHODS:Rats in the experimental group were administrated 5,10,15,20,and 25 ?g/kg HGF per 24 hours,the partes aequales sodium chloride was injected into the spontaneous hypertension and control groups.Five minutes after administration,systolic pressure and heart rates were measured.The rats were sacrificed and harvested 2 mL blood of right ventricle when blood pressure decrease the lowest,about 30 minutes after administration.MAIN OUTCOME MEASURES:The effect of HGF on systolic pressure and heart rates,and levels of serum nitrogen monoxidum(NO),plasma endothelin(ET),as well as angiotensinⅡ(Ag Ⅱ) were detected by colorimetry and radio-immunity methods.RESULTS:When injected 5?g/kg HGF,the blood pressure did not significantly change.After 10 ?g/kg HGF injection,the blood pressure began to decrease and reached a peak after 30 minutes,gradually recovered after 1 hour,and back to the normal after 5 hours.Injection of 20 ?g/kg has largest effect on rats,with reduced contractive pressure 40-50mmHg,but no significantly changes appeared by adding HGF dose.There were no significantly differences of heat rate and blood pressure between the two control groups.Compared with the spontaneous hypertension group,the levels of ET and AgⅡ were decreased,however,the level of NO was increased(P