Proteasomes is a multienzyme complex.It can degradate cyclin,which control the process of cell cycle and cell apoptosis.Proteasome inhibitor regulate cell cycle and promote cell apoptosis through suppressing UP pathway.Proteasome inhibitor can stimulate apoptosis of various hematological systemetic malignant tumor and cause cell apoptosis through different mechanism in vivo and vitro.Therefore,proteasome inhibitor is a new-style tumor targeted therapy drug.

Objective To investigate the effect of arsenic trioxide (As2O3) and imatinib mesylate (imatinib) or in combination with imatinib with different concentration on Raji cells and the mechanisms.Methods The inhibition of cell proliferation was measured by MTT assay to assess the cells survival after As2O3 and imatinib or in combination with imatinib treatment with different concentration at indicated time.Caspase-3 activity changes and the relative number of cells in different phases and the percentages of cells calculated in G1 and S phase of the cell cycle were assessed by FCM. The expression of p16 protein was analyzed by SABC immunohistochemical method. Results The results of MTT assay showed that As2O3 and imatinib or in combination with imatinib could inhibit Raji cells growth. There was clear statistical significance between the union groups and the single-drug group (P<0.05). As2O3 inducing apoptosis was accompanied by up-regulation and activation of apoptosis protein Caspase-3. The mean percentage of apoptosis cells was both in time-and dosage-dependent form (P<0.0001). While Raji cell lines were less sensitive to imatinib than arsenic trioxide (P >0.05). Further more, Combination of imatinib with As2O3 had not a synergistic inducing apoptosis effect on Raji cells (P >0.05). The optical density of p16 protein increased both in time-and dosage-dependent form with As2O3 by immunohistochemical method (P<0.05). While at higher concentration and for a longer time, imatinib could up-regulated the optical density of p16 protein. There was no obvious statistic significance for p16 protein in Raji cells with using As2O3 only compared with the unions group(P >0.05). The cell cycle was arrested at G1 phase, the number of cells G1 period increased significantly,and S phase decreased on Raji cells after As2O3 treatment. The relationship between the cellular DNA contents and the concentration of As2O3 showed a dose-and time-dependent manner (P<0.0001). But it was found that imatinib had no effect on Raji cell cycle. There was no the obvious difference (P >0.05) between two drugs unions group with only using As2O3 group. Conclusion The results showed that As2O3 exerted variable and definite effects on lymphoma Raji cells, and suggested that As2O3 might induce apoptosis and up-regulate the optical density of p16 protein and arrest cell cycle. As for Raji cells, imatinib might affect the expression of p16 protein at higher concentration. Two drugs unions had no effective and synergistic effect.

Objeetive To observe NB4 cells that is treated with both ATO and BOR.Methods MTT assay demonstrated that NB4 cell lines,growth inhibiting effect after interfered with BOR alone or BOR plus ATO.Flow cytometry detect cell cycle and apoptosis.RT-PCR method detect the expression of survivin mRNA.Results MTT assay showed depressant effect by BOR.BOR can strengthen cells,lethal effect by ATO.Flow cytometry investigate obvious apoptosis and cycle blockage of G2/M stage.RT-PCR discover that ATO or BOR can downregulate the expression of survivin mRNA alone,there is an additional effect if used them at the same time.Conclusion Combination of BOR and ATO have stronger inflictive and apoptosisinducing activity.The blockage of G2/M stage and degression of survivin mRNA is a possible mechanism that leads to cell apoptosis treated with BOR and ATO.

Objective To evaluate the clinical effects,CT features and side-effects of percutaneous microwave coagulation therapy(PMCT) in the treatment of peripheral lung cancer.Methods CT-guided PMCT was applied to 16 cases of peripheral lung cancer from August 2003 to October 2004 in this hospital.Pathological or cytological findings showed 9 cases of squamous carcinoma and 7 cases of adenocarcinoma.A needle microwave antenna was applied into the tumor percutaneously under CT guidance.In each emission of microwave,the tumor was ablated with a 2 450 Hz microwave coagulation output of 65~75 W for 3~5 min.According to the size and shape of the tumor,single or multiple ablation emission was selected.Results The operation time was(15~60) min(mean,35 min).Complete remission(CR) was achieved in 1 case,partial remission(PR) in 4 cases,and no changes(NC) in 11.Follow-up observations in the 16 cases for 3~15 months(mean,9.5 months) found 2 cases of tumor metastasis and 1 case of death.Conclusions Percutaneous microwave coagulation therapy is a safe,micro-invasive,and effective treatment for the management of peripheral lung cancer.

Objective To investigate the relationship of antishock effect of arginine vasopressin(AVP) on hemorrhagic shock and its relationship with Rho kinase.Methods Hemorrhagic shock(40 mmHg for 2 h) Wistar rats were treated respectively by AVP(0.4 U/kg),Rho kinase specific inhibitor,Y-27632(30 ?g/kg),or these 2 reagents.The pressor effect of norepinephrine(NE) on these rats and the contractility of their isolated superior mesenteric artery(SMA) were observed.Isolated SMAs from hemorrhagic shock rats were adopted to observe the effects of AVP on vascular reactivity and calcium sensitivity and its relationship to Rho kinase with an isolated organ perfusion system.Results AVP at the concentration of 0.4 U/kg significantly improved the pressor effect of NE and the contractile response of SMA.While,Y-27632(30 ?g/kg) abolished these beneficial effects of AVP.The vascular reactivity and calcium sensitivity of SMA were significantly decreased following hemorrhagic shock.AVP at the concentration of 0.5 and 5 nmol/L significantly increased the decreased vascular reactivity and calcium sensitivity.These effects of AVP were abolished by Y-27632(10 ?mol/L).Conclusion Rho kinase may take part in the action of AVP on hemorrhagic shock via improving shock induced vascular hyporeactivity and calcium desensitization.

Objective To compare the resuscitation effect of 6% hydroxyethyl starch (HES) of different molecular weight in normal saline on hemorrhagic shock in rats. Methods Hemorrhagic shock model was established in 50 SD rats by 45% hemorrhage,and then they were equally divided into 5 groups. The rats were administered with HES40/,HES130/,HES200/normal saline,Voluven or Haes. Their mean arterial blood pressure (MAP),left intraventricular systolic pressure (LVSP),the maximal change rate of left intraventricular pressure (?dp/dtmax) of hemorrhagic shock rat were observed. Meanwhile,the artery blood gas,the survival time and 24-hour survival rate were also observed. Results Similar hemodynamic parameters values were obtained in the rats treated with our HES and those with Voluven or Haes. HES130 and HES200 prolonged the survival time of shocked animals in comparison with HES40. Among the 3 types of HES,HES200 had the best effect,which is equivalent to Voluven and Haes. Conclusion HES of 3 molecular weights have beneficial effect on hemorrhagic shock,and HES200 exerts best.

AIM To investigate the role of serine/threonine protein phosphatases 1 and 2A (PP1/2A) in regulation of cell signal transduction involved in the tolerance of human umbilical vein endothelial cells (HUVEC) to hypoxia. METHODS HUVEC tolerance was established by hypoxic preconditioning. The tolerance of HUVEC was evaluated by the cell survival rate, lactic dehydrogenase (LDH) releasing and total antagonistic-oxidative capability (T-AOC). Subcellular localization of nuclear factor E2-related factor 2 (Nrf2) was determined by immunocytochemistry combined with Western blot. The expression of stress protein of heme oxygenase-1 (HO-1) was measured by Western blot. RESULTS Hypoxia 90 min decreased the survival rate and T-AOC of HUVEC significantly, increased the release of LDH in cultured HUVEC. Compared with the hypoxic group, hypoxic preconditioning (4, 8 and 24 h after hypoxia 10 min) up-regulated the tolerance against hypoxia in HUVEC, the survival rate of HUVEC and T-AOC increased and the release of LDH down-regulated when insulted with hypoxia (90 min) in HUVEC. Hypoxic preconditioning established the translocation of Nrf2 from cytoplasm to nucleus and up-regulated the expression of downstream protein HO-1. Pretreatment with okadaic acid (40 nmol·L-1), a powerful inhibitor of PP1/2A, for 10 min in hypoxic preconditioning HUVEC partly inhibited the translocation of Nrf2 from cytoplasm to nucleus and the expression of HO-1, abolished the tolerance of HUVEC established by hypoxic preconditioning. CONCLUSION PP1/2A at least partly take part in Regulation of translocation of Nrf2 and expression of HO-1, with is associated with the tolerance of HUVEC established by hypoxic preconditioning.

Objective To investigate the beneficial effects of cyclosporin A ( CsA) on traumatic hemorrhagic shock in rats. Methods The traumatic hemorrhagic shock model was adopted in 144 SD rats which were divided into 6 groups: sham-operated group,shock control group,lactated Ringer's solution ( LR) group,CsA 1 mg/kg,5 mg/kg and 10 mg/kg group. The effects of three doses of CsA on the animal survival time and 24 h survival rate were observed,and the effects of CsA on hemodynamic parameters,including mean arterial blood pressure ( MAP) ,left intraventricular systolic pressure ( LVSP) ,left ventricular end-diastolic pressure ( LVEDP) ,maximal change rate of left intraven-tricular pressure ( ± dp/dtmax ) and heart rate ( HR) were also observed. Results CsA at the concentration of 5 mg/kg and 10 mg/kg can significantly increase the survival time and 24 h survival rate of shock rats,the survival rate was increased to 56. 3% from 25% of LR group. After shock,the hemodynamic parameters were significantly decreased including MAP,LVSP and ± dp/dtmax ,LR infusion only improved the hemodynamics to some extent,which were significantly lower than those in sham-operated group. CsA (5 mg/kg and 10 mg/kg) can signifi-cantly improve the hemodynamics of shock rats including LVSP and ± dp/dtmax ,which were increased at 2 h after resuscitation as compared to LR group,and return to about normal levels. 1 mg/kg of CsA also restored the hemodynamic parameters, but there were no significant differences between CsA 1 mg/kg group and LR group. Conclusion CsA has good beneficial effect on traumatic hemorrhagic shock,and 5 mg/kg and 10 mg/kg of CsA showed a better effect.

BACKGROUND:Delayed onset muscle soreness is closely related to skeletal muscle micro-injury, but the exact mechanism of skeletal muscle micro-injury is not yet clear. OBJECTIVE:To observe the histomorphological and ultrastructure changes of skeletal muscle micro-injury models induced by eccentric exercise. METHODS: Forty male Sprague-Dawley rats were randomly divided into quiet control group, immediately after exercise group, post-exercise 24 hours group, post-exercise 48 hours group and post-exercise 72 hours group. In the latter four groups, the rats were subjected to intermittent running on the-16° slope at a speed of 16 m/min: 5 minutes movement, 2 minutes rest and totaly 120 minutes. Rats in the latter four groups were observed immediately, at 24, 48, 72 hours after exercise. RESULTS AND CONCLUSION:After eccentric exercise, the morphology and ultrastructure of rat’s skeletal muscle were both changed to different extents, and Desmin and Vimentin were dyed off for anti-desmin antibody staining at varying degrees. It indicates that one-time eccentric exercise can cause delayed skeletal muscle micro-injury.

Objective To explore the effect of ILK on myocardium contraction following hemorrhagic shock .Methods With iso-lated cardiac papillary muscle and isolated heart ,the contraction of papillary muscle and hemodynamic parameters (left intraventricu-lar systolic pressure(LVSP) ,the maximal change rate of left intraventricular pressure were measured .Results Compared with nor-mal control hearts ,ILK activity ,contractile response of cardiac papillary muscle and hemodynamic parameter were decreased signifi-cantly gradually in shock heart at the 1 ,2 h(P<0 .05) ,and the change of ILK activity was positive correlative with contractile re-sponse and hemodynamic parametert .With ILK agonist [phosphatidylinositol(3 ,4 ,5)trisphosphate ,PLTP] the dysfunction of con-tractile response and hemodynamic parameter could be improved significantly (P<0 .05) ,while these improvement could be abol-ished by ILK specific inhibitor(P<0 .05) .Conclusion ILK play important role in the regulation of cardiac contractility following hemorrhagic shock .