AIM: To investigate the relationship between vascular smooth muscle cell (VSMC) injury, organelle stress response and autophagic cell death (autophagy) and ferroptosis induced by the chemical hypoxia inducer cobalt chloride (CoCl2) through the bioinformatics analysis and in vitro cell experimentation. METHODS: The dataset GSE119226 of VSMC treated with cobalt chloride was acquired from the gene expression database (GEO). The R language was used to investigate the relationship between CoCl2 treatment and organelle stress response (Golgi stress, endoplasmic reticulum stress) and two forms of cell death (ferroptosis and autophagic cell death). With primary cultured rat VSMC (rVSMC) and CoCl2-induced anoxia model, the changes in cell viability were detected by CCK-8 method, and reactive oxygen species (ROS) levels were measured using DCFH-DA method. The expression levels of HIF-1α (a key molecule in hypoxia), Golgi stress markers GM130 and p115, endoplasmic reticulum stress markers GRP78 and CHOP, autophagy markers LC3-II / LC3-I and Beclin1, and ferroptosis markers GPx4 and xCT were detected by Western blot. The effect of inducing or inhibiting organelle stress and cell death on the CoCl2-induced cell damage was also observed. RESULTS: Differentially expressed genes analysis of GSE119226 dataset showed that CoCl2 treatment of VSMCs had significant effects on organelle function and stress response, autophagy and ferroptosis-related genes, in which endoplasmic reticulum stress, protein processing in endoplasmic reticulum, regulation of Golgi to plasma membrane protein transport, autophagy / autophagic cell death, and ferroptosis pathways were remarkably enriched. The results of in vitro experiment showed that compared with normal rVSMC, cell viability was significantly decreased after CoCl2 treatment, as well as HIF-1α protein expression and ROS levels in rVSMCs were increased. In rVSMC treated with Co-Cl2, the expression levels of Golgi structural proteins GM130 and p115 (reflecting the occurrence of Golgi stress) were decreased, while the markers GRP78 and CHOP (reflecting the occurrence of endoplasmic reticulum stress) were increased. At the same time, CoCl2 treatment also reduced the expression of autophagy markers LC3-II/LC3-I and Beclin1 (indicating the decrease levels of autophagy), while the expression of ferroptosis markers GPx4 and xCT were decreased (indicating the occurrence of ferroptosis). Compared with CoCl2 treatment group, induced Golgi stress, endoplasmic reticulum stress, or ferroptosis could further reduce cell viability, while inhibition of these processes could improve cell viability. On the other hand, increasing the level of autophagy can improve the cell viability. CONCLUSION: Hypoxia induced by cobalt chloride can lead to VSMC injury. Golgi stress, endoplasmic reticulum stress, ferroptosis, and the reduction of autophagy level play an important role in it. Inhibition of organelle stress response and ferroptosis, or increase of autophagy level can improve VSMC injury caused by cobalt chloride.

Objective To observe the improved effect of propofol on vascular hyporeactivity in septic rats and its underlying mechanism.Methods A total of 96 SD rats(12 weeks old,both genders,weighing 200～220 g)were randomly divided into sham group(n=16),sepsis group(n=16,cecal ligation and puncture),propofol group(n=16),propofol+ROCK inhibitor Y-27632 group(n=16),propofol+PKCαinhibitor GO6976 group(n=16),propofol+IP3 inhibitor 2-APB group(n=8)and propofol+gap junction inhibitor metoclopramide sodium(Movens)group(n=8).In vitro vascular ring reactivity and vascular calcium sensitivity were measured to observe the improved effects of propofol on vascular hyporeactivity in septic rats and its relationships with RhoA/ROCK,PKCα,IP3 and cell gap junction.Results Determination of in vitro vascular ring and calcium sensitivity showed that the contractile reactivity to norepinephrine(NE)and to calcium sensitivity were significantly decreased in the arterial rings isolated from the septic rats compared with those from the sham group,with the dose-response curve shifting to the right,and most significant decrease by 51.42％in the superior mesenteric artery(SMA,P＜0.05).Propofol treatment significantly improved the hyporeactivity and calcium sensitivity of the vessels isolated from the septic rats,especially those of the femoral artery with a recovery rate of 89.57％(P＜0.05).In comparison with the propofol group,the dose-response curves of the propofol+Y-27632 group and the propofol+GO6976 group were shifting to right,indicating that Y-27632 and GO6976 could significantly inhibit the amelioration of propofol on calcium sensitivity of SMA in severely septic rats with an inhibitory rate of 146.95％and 88.63％(P＜0.05),respectively.Isolated vascular reactivity measurement demonstrated that Y-27632 and Movens treatment significantly antagonized the ameliorated role of propofol on hyporeactivity of blood vessels from the septic rats with an inhibitory rate of 40.79％and 169.90％(P＜0.05),separately,while no such effect was observed in the propofol+GO6976 and propofol+2-APB groups.Conclusion Propofol treatment can significantly improve vascular hyporeactivity of septic rats,which may attribute to the increase of vascular calcium sensitivity through RhoA/ROCK pathway.

Objective To investigate the clearance capacity of cardiac resident macrophages in post-sepsis and its underlying mechanism.Methods A mouse model of sepsis was established using cecum perforation ligation.Thirty male C57BL/6 mice(8 weeks old,weighing 20～25 g)were randomly and equally divided into a sham operation group(sham group)and a model group(sepsis group).Immunofluorescence assay was employed to label the cardiomyocytes and macrophages to observe the apoptosis of cardiomyocytes and the phagocytosis by cardiac resident macrophages.Cardiac resident macrophages were extracted for transcriptomic sequencing to determine the functional changes of the cells after sepsis.Cardiac resident macrophage cell lines were established at the cellular level and served as the normal group(RAC group),and the RAC cells treated with LPS were subjected as the sepsis group(RAC+LPS group).Then the differences in the ability to clear apoptotic cardiomyocytes between the 2 groups were observed.Then DQ-BSA-RED lysosomal activity detection probe,Lyso-Sensor yellow/bule dye,ELISA,and Western blotting were applied to detect the lysosomal function of cardiac resident macrophages,activity and expression of important lysosomal hydrolases,changes in contents and related subunits of vacuolar-type adenosine triphosphatases(V-ATPase).Results Compared with the sham group,the sepsis group had larger number of apoptotic cardiomyocytes(P＜0.05)and increased phagocytosis of cardiomyocytes by cardiac macrophages(P＜0.05).The results of transcriptomic sequencing revealed a significant dysfunction of lysosome-associated functions of cardiac-resident macrophages after sepsis.In in vitro experiments,the RAC+LPS group had a reduced fragmentation capacity of apoptotic cardiomyocytes,reduction in the intensity of yellow fluorescence of lysosomes(P＜0.05),and decrease in lysosomal hydrolase activity(P＜0.05)when compared with the RAC group.In addition,LPS treatment significantly decreased the activity and expression of V-ATPase and its major subunit ATP6V1A in cardiac resident macrophages(P＜0.05).Conclusion Cardiac resident macrophages show reduced clearance of apoptotic cardiomyocytes after sepsis,which may be related to a decrease in the activity of ATP6V1A,an important subunit of its lysosomal V-ATPase,and reduced activity of lysosomal hydrolases.

Objective:To discuss the effect of fluid resuscitation on the occurrence of ferroptosis in vascular tissue and the structure of vascular cells in the rats with blast injury complicated with hemorrhagic shock,and to clarify its mechanism.Methods:A total of 54 healthy adult SD rats were randomly divided into normal group,blast injury complicated with hemorrhagic shock(model)group,and the fluid resuscitation(treatment)group,and there were 18 rats in each group.Among them,10 rats were randomly selected to observe the surival status and another 8 rats were selected to detect the other indexes.The average survival time(ST),24 h and 72 h survival rates of the rats in various groups were observed;the blood pressure(BP),heart rate(HR),and respiratory rate(RR)of the rats in various groups were observed;the levels of serum creatinine(Scr),blood urea nitrogen(BUN),lactate(LAC),glucose(GLU),iron ions,glutathione(GSH),and malondialdehyde(MDA)and the activities of aspartate aminotransferase(AST),alanine aminotransferase(ALT)and lactate dehydrogenase(LDH)in serum of the rats in various groups were detected;Western blotting method was used to detect the expression levels of ferroptosis marker proteins glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),and heme oxygenase 1(HO-1)proteins in superior mesenteric artery tissue of the rats in various groups;the pathomorphology of the superior mesenteric artery of the rats in various groups was observed.Results:All the rats in normal group survived for 72 h,while the longest ST of the rats in model group did not exceed 9 h.Compared with model group,the ST and 24 h survival rate(SR)of the rats in treatment group were significantly increased(P＜0.05).Compared with normal group,the BP,HR,and RR of the rats in model group were significantly decreased(P＜0.01).Compared with model group,the BP,HR,and RR of the rats in treatment group were significantly increased after fluid resuscitation(P＜0.05).Compared with normal group,the activities of AST and ALT,and the levels of Scr and BUN in serum of the rats in model group were significantly increased(P＜0.01).Compared with model group,the serum levels of LAC and GLU of the rats in treatment group were significantly decreased(P＜0.01).Compared with normal group,the concentration of iron ion,GSH level,MDA level,LDH activity in serum of the rats in model group were significantly increased(P＜0.05);compared with model group,the concentration of iron ion and LDH activity in serum of the rats in treatment group was significantly decreased(P＜0.01).Compared with normal group,the expression levels of GPX4 and SLC7A11 in superior mesenteric artery tissue of the rats in model group were significantly decreased(P＜0.05);compared with model group,the expression levels of GPX4 and SLC7A11 in superior mesenteric artery tissue of the rats in treatment group were significantly increased(P＜0.05).Compared with normal group,the expression level of HO-1 protein in superior mesenteric artery tissue of the rats in model group was increased(P＜0.01);compared with model group,the expression level of HO-1 protein in superior mesenteric artery tissue of the rats in treatment group was increased(P＜0.01).The microscopic pathology results showed that the cell arrangement in the layers of the superior mesenteric artery tissue of the rats in model group was disordered,the swelling was significant and the thickness was increased;the pathological changes in superior mesenteric artery tissue of the rats in treatment group was alleviated.The ultramicroscopic pathology results showed that the endothelial cell structure of blood vessels of the rats in normal group was intact,and there was no swelling in the subendothelial matrix;the vascular endothelial cell membrane of the rats in model group was damaged,there were cytoplasmic dissolution and fragmentation,and the swelling of the subendothelial matrix was significant;the swelling of the vascular endothelial cells in treatment group was alleviated.Conclusion:Ferroptosis occurs in vascular tissue of the rats with blast injury complicated with hemorrhagic shock,and fluid resuscitation can alleviate the structural damage of the vascular cells by inhibiting the vascular tissue ferroptosis.

Objective To explore the effect of training mode based on action learning on improving the practicing ability of hospital pharmacists.Methods Thirty pharmacists who received training from September 2022 to December 2023 at Panzhihua Central Hospital were randomly divided into an education reform group(16 cases)and a routine group(14 cases).The education reform group adopted a routine teaching method based on action learning,while the routine group adopted a routine teaching method.The differences between the two groups of pharmacists in theoretical knowledge,practical operation,pharmaceutical services,emergency response,and comprehensive quality were compared.Results The pharmacists in the education reform group were better than the routine group in prescription review,clinical medication analysis,pharmaceutical services,emergency response,andcomprehensive quality.The difference was statistically significant(P＜0.05).Conclusion The teaching model based on action learning can effectively enhance the higher order thinking ability of pharmacists and help them better apply medical knowledge and skills to serve patients and physicians.

OBJECTIVE To investigate the protective effects and mechanism of ziyuglycoside Ⅰ on acute lung injury in sepsis rats based on network pharmacology， and conduct experimental verification. METHODS The network pharmacology was used to predict the potential target of ziyuglycoside Ⅰ in the treatment of acute lung injury following sepsis. The rat model of sepsis was reproduced by cecum ligation and puncture for experimental verification. Totally 192 SD rats were randomly divided into the sham operation group （Sham group）， sepsis group （Sep group）， conventional therapy group （CT group） and ziyuglycoside Ⅰ group （Zg Ⅰ group）， respectively. Sham group and Sep group were given sterile normal saline， and CT group and ZgⅠ group were given relevant volume of Ringer’s solution and ziyuglycoside Ⅰ. The arterial blood gas， serum inflammatory factors， lung wet/dry mass ratio， pathological changes of lung tissue， pulmonary vascular permeability， the expressions of pulmonary vein tight junction protein 1 （ZO-1） and vascular endothelial cadherin （VE-cadherin） protein and 72-hour survival were observed in each group. RESULTS Results of network pharmacology showed that there were 47 potential targets of ziyuglycoside Ⅰ in the treatment of sepsis. The results of gene ontology function enrichment analysis and Kyoto encyclopedia of genes and genomes pathway enrichment analysis showed that the mechanism could 598486924@qq.com be correlated with biological processes such as positive regulation of reactive oxygen species metabolism， wound healing， regulation of endothelial cell proliferation， cell activation， blood vessel development， response to oxidative stress， etc.， and with signaling pathway such as apoptosis， tight junction， HIF-1 signaling pathway， etc. The results of experimental verification showed that compared with Sham group， pH value and the level of partial arterial oxygen pressure were decreased significantly in Sep group （P＜0.05）， while the level of partial pressure of carbon dioxide， serum levels of tumor necrosis factor α， interleukin 6 were increased significantly （P＜0.05）； the ratio of lung wet/dry mass was increased significantly （P＜0.05）； the protein expressions of ZO-1 and VE-cadherin were decreased significantly （P＜0.05）； 72 h survival rate decreased，the survival time was significantly shortened （P＜0.05）； the results of pathological observation of lung tissue showed that the rats’ alveoli were extensively ruptured， the alveolar wall was thickened and accompanied with edema， and there was obvious inflammatory cell infiltration； the results of pulmonary vascular permeability observation showed that the lung surface of rats was dark， with a large amount of Evans blue exudation， and the left lower lung was obviously dark blue. Compared with Sep group， the levels of above indexes almost were reversed significantly in CT group and ZgⅠ group （P＜0.05）； the lung histopathology and pulmonary vascular permeability were significantly improved， and the recovery degree of ZgⅠ group was greater than that of CT group， which was close to the results of Sham group. CONCLUSIONS Ziyuglycoside Ⅰ can significantly reduce inflammatory reaction and acute lung injury in septic rats， which is related to vascular function and tight junction signal pathway.

A female patient, years of age 56, having no distinct inducement before 5 d but developed fever, coughing, and shortness of breath, presented in People′s Hospital of Zhongshan with community-acquired pneumonia on March 3rd, 2023. Influenza A virus infection was confirmed on March 11th after performing macro transcriptome sequencing with alveolar lavage fluid, and H3N8 was confirmed with influenza typing afterward, having declared dead on March 16th. This case is a patient with refractory multiple myeloma autologous stem cell transplantation and continuous chemotherapy with immune dysfunction. She has a history of chronic upper respiratory tract infection. Imaging showed a widespread distribution of plaques, solid lesions, and other pneumonia manifestations in both lungs, a severe decrease in the counts of white blood cells, platelets, neutrophils, and lymphocytes, and a significant increase in laboratory inflammation indicators. After the clinical consideration was an acute aggravation of chronic respiratory tract infection and poor effect of anti-bacterial treatment, fungal infection was considered, and antibiotic treatment was changed several times according to the condition. Still, the outcome was poor, and the disease progressed rapidly. Medical workers initiated Oseltamivir antiviral therapy immediately after the alveolar lavage fluid etiology confirmed A-H3N8 influenza. However, due to complex and varied systemic symptoms, including inflammatory storm, sepsis, acute respiratory failure, tachycardia, coagulopathy, and other extrapulmonary organ injuries, she died 19 days after signs due to severe respiratory failure and multiple organ failure.

Objective To investigate the early resuscitation effect of hemoglobin-based oxygen carriers (HBOC) in rats with uncontrolled hemorrhagic shock.Methods 170 Sprague-Dawley (SD) rats were randomly divided into five groups:lactate Ringer solution (LR) control group,whole blood control group,and 0.5％,2.0％,5.0％ HBOC groups,with 34 rats in each group.The uncontrolled hemorrhagic shock model in SD rats was reproduced by cutting off the splenic artery branch,and induced mean arterial pressure (MAP) reducing to 40 mmHg (1 mmHg =0.133 kPa).The corresponding solution was infused after model reproduction in each group,maintaining MAP at 50 mmHg for 1 hour,then completely ligating and hemostasis,and maintaining MAP at 70 mmHg for 1 hour and 80 mmHg for 1 hour respectively,after maintaining MAP 80 mmHg,all were supplemented with LR to 2 times blood loss volume.The survival rate and blood loss rate were observed in 16 rats in each group,hemodynamics parameters including MAP,left ventricular systolic pressure (LVSP) and the maximum rate of left ventricular pressure rise (+dp/dtmax) were determined in another 10 rats,and cardiac output (CO) and tissue oxygen supply (DO2) were observed in the rest 8 rats.Results ① When resuscitation by LR alone,the blood loss rate of animals was as high as 60％ to 70％.Compared with the LR control group,whole blood recovery could significantly reduce the blood loss rate before hemostasis in uncontrolled hemorrhagic shock rats [(46.6 ± 4.5)％ vs.(62.3 ± 4.0)％,P ＜ 0.01];0.5％,2.0％,5.0％ HBOC could significantly decrease the blood loss rate,especially in 5.0％ HBOC group with significant difference as compared with that in the LR control group [(45.6±4.1)％ vs.(62.3±4.0)％,P ＜ 0.01].② When LR was used alone for resuscitation,the rats died quickly and survived for a short time.Only one rat survived for 12 hours,and no rat survived for more than 24 hours.Compared with the LR control group,whole blood resuscitation could improve the survival rate of uncontrolled hemorrhagic shock rats,and the survival time was significantly prolonged (hours:20.4± 4.6 vs.3.5 ± 1.1,P ＜ 0.01);0.5％,2.0％ and 5.0％ HBOC also significantly prolonged the survival time of rats.The 5.0％ HBOC group had the best effect,4 rats survived in 24 hours,and the survival time was significantly longer than that of the LR control group (hours:18.4 ± 4.0 vs.3.5 ± 1.1,P ＜ 0.01),and it was the same as the whole blood control group.③ Compared with pre-shock,CO,DO2 and hemodynamic parameters of uncontrolled hemorrhagic shock rats were significantly decreased,and the above parameters were gradually increased with the prolongation of rehydration time.Compared with the LR control group,whole blood resuscitation could significantly increase CO and DO2,and improve hemodynamics in rats with uncontrolled hemorrhagic shock at different time points.Three concentrations of HBOC could also increase CO,DO2 and other hemodynamic parameters of rats at 1 hour of maintaining MAP of 80 mmHg after hemostasis and 1 hour and 2 hours after resuscitation.The effect of 5.0％ HBOC group was more significant than that of the LR control group with statistically significant difference [CO (× 10-3,L/min):72.84±2.84 vs.63.11±2.38 at 1 hour of maintaining MAP of 80 mmHg,70.25±4.55 vs.59.88 ± 9.31 at 1 hour after resuscitation,71.51 ± 2.90 vs.53.24 ± 6.32 at 2 hours after resuscitation;DO2 (L· min-1 · m-2):271.9± 13.5 vs.159.1 ±25.4 at 1 hour of maintaining MAP of 80 mmHg,261.0± 15.0 vs.145.7±20.1 at 1 hour after resuscitation,249.6± 12.0 vs.107.4± 18.2 at 2 hours after resuscitation;MAP (mmHg):82.1±2.1 vs.74.0±2.8 at 1 hour of maintaining MAP of 80 mmHg,107.5±9.3 vs.64.0±5.7 at 1 hour after resuscitation,104.0±9.7 vs.73.0±4.2 at 2 hours after resuscitation;LVSP (mmHg):128.6±7.9 vs.103.8±0.8 at 1 hour of maintaining MAP of 80 mmHg,129.3±± 15.0 vs.99.4±0.0 at 1 hour after resuscitation,127.5± 11.3 vs.97.4±0.0 at 2 hours after resuscitation;+dp/dt max (mmHg/s):6 534.2±± 787.6 vs.5 074.0± 71.7 at 1 hour of maintaining MAP of 80 mmHg,5 961.5 ±± 545.4 vs.4 934.5 ± 510.2 at 1 hour after resuscitation,5 897.4± 350.5 vs.4 534.7 ±489.2 at 2 hours after resuscitation,all P ＜ 0.05].Conclusions HBOC infusion prolonged the survival time,increased survival rate,and improved hemodynamics,cardiac function and tissue oxygen supply in a dose-dependent manner in the early stage of uncontrolled hemorrhagic shock.The recovery effect of 5.0％ HBOC was similar to that of the whole blood.

Objective To observe the protective effects of calcium-sensing receptor (CaSR) inhibitor Calhex231 on traumatic hemorrhagic shock rats. Methods 144 SD rats were divided into six groups by random number table method: normal group, shock group, lactated Ringer's solution (LR) group, LR + Calhex231 0.1 mg/kg group, LR + Calhex231 1 mg/kg group, and LR + Calhex231 5 mg/kg group, with 16 rats in each group for survival observation and 8 rats for hemodynamics test. 64 SD rats were divided into four groups: normal group, shock group, lactated Ringer's solution (LR) group, LR + Calhex231 1 mg/kg group, with 8 rats in each group for detecting organ blood flow and superior mesenteric artery vascular reactivity and the other 8 rats for mesenteric artery vascular reactivity. After the establishment of traumatic hemorrhagic shock model, the shock group did not receive resuscitation, and the LR group was resuscitated with LR equal to two times of the blood loss volume. The three LR + Calhex231 groups with different dosages were firstly given LR of equal volume to that of blood loss, and then the Calhex231 was dissolved into LR (equal to the blood loss volume) to resuscitate. The wound was ligated and sutured immediately after resuscitation. The effect of Calhex231 on animal's 24-hour survival since the beginning of resuscitation was observed. The hemodynamics including the mean arterial blood pressure (MAP), left intraventricular systolic pressure (LVSP), maximal rising, and declining rate of left intraventricular pressure (±dp/dtmax) were observed before shock, at the end of shock, 1 hour after resuscitation, and 2 hours after resuscitation. The effects of Calhex231 on vital organ blood flow and vascular reactivity were observed 2 hours after resuscitation. Results All the shock rats died within 9 hours after the shock model was established. The survival outcomes of LR group rats were slightly improved compared with the shock group rats(P ＜0.05). The survival time and 24 hour survival rate of LR + Calhex231 1 mg/kg group and LR + Calhex231 5 mg/kg group rats were significantly increased compared with the shock group rats (P ＜0.05). The hemodynamic indexes of LR + Calhex231 groups were higher than those of the LR group. The best effect was observed in LR + Calhex231 1 mg/kg group rats (P ＜ 0.01). The MAP, LVSP and ± dp/dtmax were restored to normal level (64.9％, 82.4％, 89.8％, and 77.8％, respectively). Meanwhile, the blood flow in liver and kidney of LR + Calhex231 1 mg/kg group rats were increased from 57.2％ and 41％ to 108.7％ and 95.1％, respectively. The vascular reactivity including superior mesenteric artery and mesenteric artery of LR + Calhex231 1 mg/kg group rats were also increased (P ＜0.01). Conclusions In rats with hemorrhagic shock, the calcium sensitive receptor inhibitor Calhex231 can improve the vascular reactivity, the hemodynamics, and the blood flow of important organs. It plays a role in protecting the cardiovascular function and reducing the mortality after traumatic hemorrhagic shock.

Objective To investigate the mechanism of interleukin-1β(IL-1β) mediating the vascular calcium desensitization of septic rats by down-regulating Rho kinase activity.Methods Thirty-two SD rats were randomly divided into the sham operation group,cecal ligation and puncture (CLP) 3 h group,CLP 6 h group and CLP 12 h group,8 cases in each group.The septic rat was duplicated by CLP.Then the plasma IL-1β level and calcium sensitivity of superior mesenteric arteries (SMAs) were detected at different time points.Their correlation was analyzed.VSMCc derived from SMAs were cultured and incubated with different concentrations of human recombinant IL-1β for 24 h.Then the influences of IL-1β on the MLC20 phosphorylation level,Rho kinase activity,G protein expression level and RhoGEF activity were observed.Results The calcium sensitivity of SMAs after CLP 3 h began to decrease(P＜0.05),while plasma IL-1β level began to increase after CLP 6 h (P＜0.05),the change trend of SMAs calcium sensitivity was negatively correlated with plasma IL-1β level change(P＜0.05).IL-1β could decrease the phosphorylation level of VSMCs myosin light chain(MLC20) and Rho kinase activity(P＜0.05),up-regulate Gα11 expression and down-regulate Gα12 expression,but had no obvious effect on Gαq and Gα13 expression(P＞0.05).IL-1β could significantly reduce RhoGEF and PDZ-RhoGEF activity(P＜0.05) but significantly increase p63 Rho GEF activity(P＜0.05).Conclusion IL-1β induces the decrease of PDZ-RhoGEF and Rho kinase activity by down-regulating Gα12 expression,causes the decrease of MLC20 phosphorylation level,thus mediates the occurrence of calcium desensitization in septic rat;in addition,IL-1β may cause the increase of p63 RhoGEF activity by upregulating Gα11 expression,thus mediates the increase of vascular calcium sensitivity in septic rats,but the total effect is the decrease of calcium sensitivity.