Improved effect and mechanism of propofol on vascular hyporeactivity in septic rats / 陆军军医大学学报

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.

Involvement of intracellular organelle stress, autophagy and ferroptosis in cobalt chloride-induced vascular smooth muscle cell injury / 中国临床药理学与治疗学

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.

Study on protective effects and mechanism of ziyuglycoside Ⅰ on acute lung injury in sepsis rats / 中国药房

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.

Scoring methods in injury assessment of rats with trauma combined with seawater immersion / 中华创伤杂志

Objective:To explore and establish the scoring method of injury assessment in rats with trauma combined with seawater immersion, so as to provide a reference for injury assessment in the special environment of trauma combined with seawater immersion.Methods:Sixty-four SD rats were divided into two groups according to the random number table, including hemorrhagic shock group and compound injury group, with 32 rats per group. Each group was divided into trauma combined with seawater immersion group and simple trauma group, with 16 rats per group. In trauma combined with seawater immersion group, the hemorrhagic shock model was placed in 15℃ seawater for 1 hour to start bleeding, and the blood loss was 30% of the total blood volume. The composite injury model caused 10% Ⅱ degree burns and was incised along the vental midline with a length of about 2 cm, and then placed in 15℃ seawater for 1 hour. The death and survival time were recorded.The survival time significantly longer than 4 hours out of water was recorded as survival, and significantly shorter than 4 hours out of water was recorded as death. Data were observed within 9 hours after injury, including the changes of physiological indexes (respiration, blood pressure, anal temperature) and arterial blood gas (blood glucose, pH value, blood lactic acid, arterial oxygen partial pressure, arterial carbon dioxide partial pressure, bicarbate, sodium ion, chloride ion, calcium ion, potassium ion). Each index were compared between trauma combined with seawater immersion group and simple trauma group. According to the survival situation of all the trauma combined with seawater immersion group at 4 hours out of water, the rats were divided into survival group and death group. The indicators affecting survival were screened, and then the scatter plot of each index corresponding to the mortality rate was established. According to the trend of each index in different interval in the scatter chart, the score table of injury condition was established.Results:The total mortality was 28% (9/32) in trauma combined with seawater immersion group, and was 6% (2/32) in simple trauma group ( P<0.05). The survival time in trauma combined with seawater immersion group [(8.1±3.7)hours] was shorter than that in simple trauma group [(11.3±4.8)hours] ( P<0.05). In trauma combined with seawater immersion group, the respiratory rate[(58.8±2.9)times/min] was slower than that in simple trauma group [(100.4±7.2)times/min], blood pressure [(80.0±25.1)mmHg] was lower than that in simple trauma group [(89.8±18.1)mmHg], and anal temperature [22.4(20.1, 25.0)℃] was significantly lower than that in sample trauma group [31.7(30.5, 33.2)℃], pH value (7.1±0.1) was lower than that in simple trauma group (7.3±0.1), and arterial oxygen partial pressure [(196.3±34.1)mmHg], arterial carbon dioxide partial pressure [45.5(35.1, 51.1)mmHg], serum sodium [145(142, 148)mmol/L], serum chlorine [120(115, 125)mmol/L], serum calcium [(1.3±0.1)mmol/L]as well as serum potassium [(3.6±0.8)mmol/L] were higher than those in simple trauma group [(149.4±22.6)mmHg, 29.7(25.6, 34.5)mmHg, 142(139, 144)mmol/L, 118(114, 121)mmol/L, (1.2±0.1)mmol/L, (3.3±0.6)mmol/L] (all P<0.05). There were no significances in other indexes between the two groups ( P>0.05). In death group, the breathing[36(30, 36)times/min], blood pressure [(43.1±21.8)mmHg], anal temperature [(20.0±1.9)℃], pH value (7.1±0.1), and bicarbonate [(12.3±2.2)mmol/L] were significantly inhibited or suppressed compared with survival group [60(48, 78)times/min, (86.6±19.3)mmHg, (23.0±3.1)℃, 7.2±0.1, (14.6±2.3)mmol/L (all P<0.05). While the two groups showed no significant differences in other indices ( P>0.05). Therefore, the respiration, blood pressure, rectal temperature, pH value and bicarbonate that significantly affect the survival of rats were screened. According to the death rate corresponding to different intervals, a score value was assigned to the interval as the weight of its impact on survival, namely on the severity of the injury, and an injury score table for trauma combined with seawater immersion in rats was established. The injury scoring scale <6 points indicated no death, 6-9 points indicated the mortality of 50%, ≥9 points indicated the mortality of 71%. The 6 points and 9 points were cutoff value of the scale. It can be considered that the scale of <6 points was classified as minor injury, 6-9 points as moderate injury, and ≥9 points as severe injury. Conclusions:The seawater immersion can result in reduced survival time and increased early mortality, manifested as respiratory depression, more serious blood loss, severe hypothermia, severe metabolic acidosis, water and electrolyte disorders (high sodium, high chlorine, high calcium, and high potassium), etc. According to the respiration, blood pressure, anal temperature, pH value and bicarbate, which affect the survival of rats, the injury rating scale of rats with trauma combined with seawater immersion can be established by using the scatter chart. The predicted mortality rate by using the rating scale was roughly consistent with the actual mortality rate, so the injury rating scale basically had a good prediction and hint for the trauma rats combined with seawater immersion.

Highlights and progress in medical research of trauma emergency care in domestic and abroad during "13th Five-year Plan" period / 中华创伤杂志

Trauma, a major public hazard in modern society, results in 3.5-5.8 million deaths each year. Governments all over the world pay high attention to the prevention and treatment of trauma, and have established corresponding emergency rescue organizations and rescue teams, with corresponding emergency rescue modes and prevention and treatment measures proposed. China has made great achievement in trauma care. The author reviewes the progress in trauma in domestic and abroad during "13th Five-Year Plan" period in aspects of the injury assessment, on-the-spot emergency care, early treatment, and early warning and intervention of associated complications, so as to provide references for trauma care.

Advances in molecular, biochemical and immunological diagnosis of tuberculous pleurisy / 中华临床感染病杂志

Tuberculous pleurisy (TP) is a common disease, especially in areas with high prevalence of tuberculosis. However, because of the lack of bacterial characteristics in pleural effusion, the detection sensitivity of traditional smear and culture method is low, and the pleural biopsy has certain risks; therefore, the diagnosis of tuberculous pleurisy is challenging. Due to the limitations of traditional detection methods, to find a fast, accurate and effective method for TP diagnosis is important. This article reviews the progress of molecular, biochemical and immunological methods for diagnosis of TP.

Beneficial effects of hemoglobin-based oxygen carriers on early resuscitation in rats with uncontrolled hemorrhagic shock / 中华危重病急救医学

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.

Protective effect of calcium-sensing receptor inhibitor Calhex231 on traumatic hemorrhagic shock rats / 中华创伤杂志

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.

Study on mechanism of IL-1β mediating vascular calcium desensitization in septic rats through down-regulating Rho kinase activity / 重庆医学

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.

Study on mechanism of IL-1β mediating vascular calcium desensitization in septic rats through down-regulating Rho kinase activity / 重庆医学

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.