Objectives.To study the expression of TNF α mRNA and the effect of somatostatin on the expression of TNF α mRNA in multiorgans of rats with acute hemorrhagic necrotic pancreatitis(AHNP). Methods.AHNP in the rat was ...Objectives.To study the expression of TNF α mRNA and the effect of somatostatin on the expression of TNF α mRNA in multiorgans of rats with acute hemorrhagic necrotic pancreatitis(AHNP). Methods.AHNP in the rat was induced by retrograde injection of 5% sodium taurocholate into the bile-pancreatic duct. Somatostatin octapeptide (SS-OP) (2μg/kg)was injected into the femoral vein imme- diately in rats of the treatment group after inductive AHNP. Rats of the sham operative group received in- jection of saline. Sixty animals of the AHNP and sham operative groups at the designated time(0. 2h, 0. 5 h, 2h, 4h, 8h, after the operation,six animals at each time point)and tweleve animals of treatment group at 4h after the operation were sacrificed for samples of pancreas, liver and lung. The expressions of TNF α mRNA within the pancreas, liver and lung were established by RT－PCR. Results. TNF α mRNA became detectable in the pancreas as early as 0. 2h after inductive AHNP, while it was undetectable in other organs until 0. 5h. Expression of TNF α mRNA in each tissue increased continuously and reached a peak at 4h,demonstrating a significant difference compared with that at 0. 5h and 8h. Expressions of TNF α mRNA from pancreas, liver and lung were decreased 50-80% in the treat- ment group, the pancreatic necrosis was also attenuated dramatically. Conclusion. TNF α mRNA was detectable in pancreas,liver and lung tissues at the early stage of AH- NP.SS-OP can significantly inhibit the expression of TNF α mRNA and attenuate the pancreatic necrosis. We feel that this may be an important mechanism of SS-OP in the treatment of AHNP.展开更多
BACKGROUND: Toll-like receptor (TLR) 2/4 might play important roles in mediating proinflammatory cytokine synthesis and release. And nitric oxide (NO) has been used to treat acute respiratory distress syndrome (ARDS)....BACKGROUND: Toll-like receptor (TLR) 2/4 might play important roles in mediating proinflammatory cytokine synthesis and release. And nitric oxide (NO) has been used to treat acute respiratory distress syndrome (ARDS). This study aimed to investigate the changes in TLR2/4 gene expression in the lungs of rats with acute lung injury (ALI) complicated by acute hemorrhage necrotizing pancreatitis (AHNP) and the effect of NO on the TLR2/4 gene expression. METHODS: One hundred and ten SD male rats were randomly divided into sham-operated group ( n = 10) , AHNP group (n = 30) , chloroquine-treated group ( n = 30) , and L-Arg-treated group (n =40). The lungs were dissected for lung histological scoring, and bronchoalveolar lavages were harvested for lung injury indexing. TLR2/4 mRNA expression in the lungs was measured by RT-PCR. RESULTS: TLR2/4mRNA was detected in the lungs with low values in the sham-operated group (0.016±0. 210E-2, 0.112 ±0.750E-2) , but it was markedly increased at 3 hours in the AHNP group (0.787±0.751E-2, 1.512 ±1.794E-2) , peaking at 12 hours (1.113 ±6.141E-2, 2.957±2.620E-2; P <0.05 or P <0.01). When lung injuries were aggravated, TNF-α concentrations in the lungs were increased, but NO concentrations were decreased ( P < 0.05 or P < 0.01 ) . When TLR2/4mRNA was inhibited by CQ (3h: 0.313 ± 5.491E-2, 0.005 ±1.419E-3 ; 6h: 0.488 ±7.442E-2, 0.010 ± 1.518E-3; 12h: 0.883 ± 8.911E-2, 0.024 ± 2.760E-3; P< 0.05 or P <0.01) , lung injuries were relieved. NO concentrations in the lungs were increased but TNF-α concentrations were decreased (P <0. 05 or P <0.01). When the rats with AHNP were treated with L-Arg, TLR2/4mRNA expression in the lungs could be effectively inhibited (50mg-T: 0.656 ±3. 977E-2, 1. 501 ±6.111E-2; 100mg-T: 0.260± 0.891E-2, 0.732 ±5.135E-2; 200mg-T: 0.126 ±0.914E-2, 0.414 ± 1.678E-2; 400mg-T: 0.091 ±0.399E-2, 0.287 ± 0.176E-2; P <0.05 or P <0. 01) and lung injuries were relieved. At the same time, NO concentrations in the lungs were markedly increased, but TNF-α concentrations were decreased (P <0.05 or P <0.01). CONCLUSIONS: The expression of TLR2/4mRNA is increased in the lungs in rats with AHNP and lung injuries are aggravated. TLR2/4mRNA gene expression of the lungs of rats with AHNP could be markedly inhibited by NO, leading to the relief of lung injuries.展开更多
Summary： This study preliminarily investigated the mechanism by which chloroquine （CQ） relieves acute lung injury （ALI） complicated in acute hemorrhagic necrotizing pancreatitis （AHNP）. Sixty male Wistar rats w...Summary： This study preliminarily investigated the mechanism by which chloroquine （CQ） relieves acute lung injury （ALI） complicated in acute hemorrhagic necrotizing pancreatitis （AHNP）. Sixty male Wistar rats were randomized into sham-operated group （group A, n=10）, AHNP group （group B, n=10）, L-arginine-treated group （group C, n=10）, L-N-nitro-L-arginine methyl ester （NAME）-treated group （group D, n=10）, CQ-treated group （group E, n=10） and CQ＋L-NAME-treated group （group F, n=10）. TLR4 expression was measured by using real time-PCR and Western blotting respectively. The results showed that, in the group B, the expression of TLR4 and the levels of TNF-α and IL-6 in the lungs were significantly increased, and the nitric oxide （NO） concentration was reduced, as compared with those in the group A （P〈0.05 or P〈0.01）. Lung injury was aggravated with the increased expression of TLR4. When the inhibitor and stimulator of TLR4, namely L-Arg and L-NAME, were added respectively, lung injury was correspondingly relieved or aggravated （P〈0.05 or P〈0.01）. In the group E, TLR4 expres- sion was substantially lower and NO concentration higher than those in the group B （P〈0.05 or P〈0.01）. However, in the group F, NO concentration was markedly decreased, and the inhibitory effect of CQ on TLR4 expression and the relief of lung injury were weakened when compared with those in the group E （P〈0.05 or P〈0.01）. It was concluded that TLR4 may play an important role in the pathogenesis and development of ALl complicated in AHNP. CQ could relieve ALl by decreasing the TLR4 expression and increasing the NO release.展开更多
Objective:To analyse the factors affecting the mortality of acute hemorrhagic necrotizing pancreatitis (AHNP). Methods:One hundred and twelve patients with AHNP were retrospectively divided into two groups——the dead...Objective:To analyse the factors affecting the mortality of acute hemorrhagic necrotizing pancreatitis (AHNP). Methods:One hundred and twelve patients with AHNP were retrospectively divided into two groups——the dead and survivors. Some parameters were analysed statistically.Results:The average age,sex ratio and onset of illness were similar between two groups. The difference of early shock, early ARDS, high body temperature, leukocytosis and high blood glucose between two groups were not significant. The important factors affecting the mortality were: severe pancreatic necrosis; incorrect therapeutic surgery;improper surgical methods.Conclusion: The patients with mild or moderate AHNP should mainly receive conservative treatment for 48～72 hours. The early shock and ARDS should be corrected before surgical intervention, the swelling pancreas should be dissected fully and duodenostomy should be performed in operation.展开更多
Objective In order to determine serum myelin basic protein (MBP) in patients with severe acute pancreatitis and evaluate its clinical significance. Methods\ Serum MBP was measured in 20 patients with acute hemorrhagi...Objective In order to determine serum myelin basic protein (MBP) in patients with severe acute pancreatitis and evaluate its clinical significance. Methods\ Serum MBP was measured in 20 patients with acute hemorrhagic necrotic pancreatitis (AHNP) and in 20 normal subjects by enzyme linked immunoabsorbent assay. Results\ Serum MBP content of AHNP group was significantly higher than that of normal control group (P<0.05). Serum MBP content in patients with pancreatic encephalopathy (PE) was significantly higher than that of those without PE (P<0.05). Conclusion\ ①Serum MBP content in patients with AHNP increased significantly;②Serum MBP content may reflect brain injury and its severity;③The prognosis of AHNP is correlated with its serum MBP content.\;展开更多
背景急性出血坏死型胰腺炎是临床常见的消化系统急症,肺损伤是其常见并发症和致死原因.黄芪注射液具有调节内分泌、增强免疫力、抑制病毒、抗炎、抗氧化应激等作用,但目前尚未见关于黄芪注射液在重症急性胰腺炎肺损伤中的相关研究.目的...背景急性出血坏死型胰腺炎是临床常见的消化系统急症,肺损伤是其常见并发症和致死原因.黄芪注射液具有调节内分泌、增强免疫力、抑制病毒、抗炎、抗氧化应激等作用,但目前尚未见关于黄芪注射液在重症急性胰腺炎肺损伤中的相关研究.目的分析黄芪注射液通过调控雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)/核糖体70S小亚基S6蛋白激酶(ribosome 70S small subunit S6 protein kinase,p70S6K)信号通路对急性出血坏死型胰腺炎(acute hemorrhagic necrotic pancreatitis,AHNP)肺损伤炎症反应的影响.方法48只成年SD大鼠简单随机化分为对照组、模型组、低、中、高黄芪注射液组、阳性对照组,各8只,记录各组胰腺与肺组织组织病理学变化,比较各组Schmidt评分、血清淀粉酶(amylase,AMS)Hofouaer评分、动脉血二氧化碳分压(PaCO_(2))、动脉血氧分压(PaO_(2))、炎症因子[肿瘤坏死因子-α(tumor necrosis factor-alpha,TNF-α)、白介素-6(interleukin-6,IL-6)]、mTOR/p70S6K信号通路蛋白[mTOR、p70S6K、p-p70S6K、p-mTOR、真核启动因子4E结合蛋白1(p-4E binding protein 1,4EBP1)]水平.结果对照组胰腺、肺组织无异常变化;模型组胰腺实质呈片状坏死、充血水肿,胰腺腺泡细胞与间质细胞大量破坏,小叶结构紊乱,大量炎症细胞浸润与红细胞溢出,肺泡结构排卵紊乱、间质水肿、炎性细胞浸润、肺泡间隔增宽、灶性或片状肺不张、出血;低、中、高黄芪注射液组胰腺与模型组相比,呈现出不同程度改善,且随黄芪注射液剂量增加,改善程度依次增加,其中高黄芪注射液组与阳性对照组组织病理呈现出相似特征;模型组Schmidt评分、AMS、Hofouaer评分PaCO_(2)均高于对照组,PaO_(2)均低于对照组(P<0.05);低、中、高黄芪注射液组Schmidt评分、AMS、Hofouaer评分PaCO_(2)依次降低,PaO_(2)依次升高(P<0.05);模型组TNF-α、IL-6高于对照组(P<0.05);低、中、高黄芪注射液组TNF-α、IL-6依次降低(P<0.05);模型组mTOR、p70S6K、p-p70S6K、p-mTOR、4EBP1高于对照组(P<0.05);低、中、高黄芪注射液组mTOR、p70S6K、p-p70S6K、p-mTOR、4EBP1依次降低(P<0.05).结论黄芪注射液可呈剂量依赖性改善AHNP血气指标、炎症反应、胰腺与肺组织病理状态,其机制可能是通过调控mTOR/p70S6K信号通路实现的,抑制mTOR/p70S6K信号通路可能为AHNP肺损伤的治疗提供了一个新思路.展开更多
文摘Objectives.To study the expression of TNF α mRNA and the effect of somatostatin on the expression of TNF α mRNA in multiorgans of rats with acute hemorrhagic necrotic pancreatitis(AHNP). Methods.AHNP in the rat was induced by retrograde injection of 5% sodium taurocholate into the bile-pancreatic duct. Somatostatin octapeptide (SS-OP) (2μg/kg)was injected into the femoral vein imme- diately in rats of the treatment group after inductive AHNP. Rats of the sham operative group received in- jection of saline. Sixty animals of the AHNP and sham operative groups at the designated time(0. 2h, 0. 5 h, 2h, 4h, 8h, after the operation,six animals at each time point)and tweleve animals of treatment group at 4h after the operation were sacrificed for samples of pancreas, liver and lung. The expressions of TNF α mRNA within the pancreas, liver and lung were established by RT－PCR. Results. TNF α mRNA became detectable in the pancreas as early as 0. 2h after inductive AHNP, while it was undetectable in other organs until 0. 5h. Expression of TNF α mRNA in each tissue increased continuously and reached a peak at 4h,demonstrating a significant difference compared with that at 0. 5h and 8h. Expressions of TNF α mRNA from pancreas, liver and lung were decreased 50-80% in the treat- ment group, the pancreatic necrosis was also attenuated dramatically. Conclusion. TNF α mRNA was detectable in pancreas,liver and lung tissues at the early stage of AH- NP.SS-OP can significantly inhibit the expression of TNF α mRNA and attenuate the pancreatic necrosis. We feel that this may be an important mechanism of SS-OP in the treatment of AHNP.
基金This work was supported by a grant from the National Natural Science Foundation of China (No. 30200272).
文摘BACKGROUND: Toll-like receptor (TLR) 2/4 might play important roles in mediating proinflammatory cytokine synthesis and release. And nitric oxide (NO) has been used to treat acute respiratory distress syndrome (ARDS). This study aimed to investigate the changes in TLR2/4 gene expression in the lungs of rats with acute lung injury (ALI) complicated by acute hemorrhage necrotizing pancreatitis (AHNP) and the effect of NO on the TLR2/4 gene expression. METHODS: One hundred and ten SD male rats were randomly divided into sham-operated group ( n = 10) , AHNP group (n = 30) , chloroquine-treated group ( n = 30) , and L-Arg-treated group (n =40). The lungs were dissected for lung histological scoring, and bronchoalveolar lavages were harvested for lung injury indexing. TLR2/4 mRNA expression in the lungs was measured by RT-PCR. RESULTS: TLR2/4mRNA was detected in the lungs with low values in the sham-operated group (0.016±0. 210E-2, 0.112 ±0.750E-2) , but it was markedly increased at 3 hours in the AHNP group (0.787±0.751E-2, 1.512 ±1.794E-2) , peaking at 12 hours (1.113 ±6.141E-2, 2.957±2.620E-2; P <0.05 or P <0.01). When lung injuries were aggravated, TNF-α concentrations in the lungs were increased, but NO concentrations were decreased ( P < 0.05 or P < 0.01 ) . When TLR2/4mRNA was inhibited by CQ (3h: 0.313 ± 5.491E-2, 0.005 ±1.419E-3 ; 6h: 0.488 ±7.442E-2, 0.010 ± 1.518E-3; 12h: 0.883 ± 8.911E-2, 0.024 ± 2.760E-3; P< 0.05 or P <0.01) , lung injuries were relieved. NO concentrations in the lungs were increased but TNF-α concentrations were decreased (P <0. 05 or P <0.01). When the rats with AHNP were treated with L-Arg, TLR2/4mRNA expression in the lungs could be effectively inhibited (50mg-T: 0.656 ±3. 977E-2, 1. 501 ±6.111E-2; 100mg-T: 0.260± 0.891E-2, 0.732 ±5.135E-2; 200mg-T: 0.126 ±0.914E-2, 0.414 ± 1.678E-2; 400mg-T: 0.091 ±0.399E-2, 0.287 ± 0.176E-2; P <0.05 or P <0. 01) and lung injuries were relieved. At the same time, NO concentrations in the lungs were markedly increased, but TNF-α concentrations were decreased (P <0.05 or P <0.01). CONCLUSIONS: The expression of TLR2/4mRNA is increased in the lungs in rats with AHNP and lung injuries are aggravated. TLR2/4mRNA gene expression of the lungs of rats with AHNP could be markedly inhibited by NO, leading to the relief of lung injuries.
基金supported by the National Natural Science Foundation of China (No. 81201554)
文摘Summary： This study preliminarily investigated the mechanism by which chloroquine （CQ） relieves acute lung injury （ALI） complicated in acute hemorrhagic necrotizing pancreatitis （AHNP）. Sixty male Wistar rats were randomized into sham-operated group （group A, n=10）, AHNP group （group B, n=10）, L-arginine-treated group （group C, n=10）, L-N-nitro-L-arginine methyl ester （NAME）-treated group （group D, n=10）, CQ-treated group （group E, n=10） and CQ＋L-NAME-treated group （group F, n=10）. TLR4 expression was measured by using real time-PCR and Western blotting respectively. The results showed that, in the group B, the expression of TLR4 and the levels of TNF-α and IL-6 in the lungs were significantly increased, and the nitric oxide （NO） concentration was reduced, as compared with those in the group A （P〈0.05 or P〈0.01）. Lung injury was aggravated with the increased expression of TLR4. When the inhibitor and stimulator of TLR4, namely L-Arg and L-NAME, were added respectively, lung injury was correspondingly relieved or aggravated （P〈0.05 or P〈0.01）. In the group E, TLR4 expres- sion was substantially lower and NO concentration higher than those in the group B （P〈0.05 or P〈0.01）. However, in the group F, NO concentration was markedly decreased, and the inhibitory effect of CQ on TLR4 expression and the relief of lung injury were weakened when compared with those in the group E （P〈0.05 or P〈0.01）. It was concluded that TLR4 may play an important role in the pathogenesis and development of ALl complicated in AHNP. CQ could relieve ALl by decreasing the TLR4 expression and increasing the NO release.
文摘Objective:To analyse the factors affecting the mortality of acute hemorrhagic necrotizing pancreatitis (AHNP). Methods:One hundred and twelve patients with AHNP were retrospectively divided into two groups——the dead and survivors. Some parameters were analysed statistically.Results:The average age,sex ratio and onset of illness were similar between two groups. The difference of early shock, early ARDS, high body temperature, leukocytosis and high blood glucose between two groups were not significant. The important factors affecting the mortality were: severe pancreatic necrosis; incorrect therapeutic surgery;improper surgical methods.Conclusion: The patients with mild or moderate AHNP should mainly receive conservative treatment for 48～72 hours. The early shock and ARDS should be corrected before surgical intervention, the swelling pancreas should be dissected fully and duodenostomy should be performed in operation.
文摘Objective In order to determine serum myelin basic protein (MBP) in patients with severe acute pancreatitis and evaluate its clinical significance. Methods\ Serum MBP was measured in 20 patients with acute hemorrhagic necrotic pancreatitis (AHNP) and in 20 normal subjects by enzyme linked immunoabsorbent assay. Results\ Serum MBP content of AHNP group was significantly higher than that of normal control group (P<0.05). Serum MBP content in patients with pancreatic encephalopathy (PE) was significantly higher than that of those without PE (P<0.05). Conclusion\ ①Serum MBP content in patients with AHNP increased significantly;②Serum MBP content may reflect brain injury and its severity;③The prognosis of AHNP is correlated with its serum MBP content.\;
文摘背景急性出血坏死型胰腺炎是临床常见的消化系统急症,肺损伤是其常见并发症和致死原因.黄芪注射液具有调节内分泌、增强免疫力、抑制病毒、抗炎、抗氧化应激等作用,但目前尚未见关于黄芪注射液在重症急性胰腺炎肺损伤中的相关研究.目的分析黄芪注射液通过调控雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)/核糖体70S小亚基S6蛋白激酶(ribosome 70S small subunit S6 protein kinase,p70S6K)信号通路对急性出血坏死型胰腺炎(acute hemorrhagic necrotic pancreatitis,AHNP)肺损伤炎症反应的影响.方法48只成年SD大鼠简单随机化分为对照组、模型组、低、中、高黄芪注射液组、阳性对照组,各8只,记录各组胰腺与肺组织组织病理学变化,比较各组Schmidt评分、血清淀粉酶(amylase,AMS)Hofouaer评分、动脉血二氧化碳分压(PaCO_(2))、动脉血氧分压(PaO_(2))、炎症因子[肿瘤坏死因子-α(tumor necrosis factor-alpha,TNF-α)、白介素-6(interleukin-6,IL-6)]、mTOR/p70S6K信号通路蛋白[mTOR、p70S6K、p-p70S6K、p-mTOR、真核启动因子4E结合蛋白1(p-4E binding protein 1,4EBP1)]水平.结果对照组胰腺、肺组织无异常变化;模型组胰腺实质呈片状坏死、充血水肿,胰腺腺泡细胞与间质细胞大量破坏,小叶结构紊乱,大量炎症细胞浸润与红细胞溢出,肺泡结构排卵紊乱、间质水肿、炎性细胞浸润、肺泡间隔增宽、灶性或片状肺不张、出血;低、中、高黄芪注射液组胰腺与模型组相比,呈现出不同程度改善,且随黄芪注射液剂量增加,改善程度依次增加,其中高黄芪注射液组与阳性对照组组织病理呈现出相似特征;模型组Schmidt评分、AMS、Hofouaer评分PaCO_(2)均高于对照组,PaO_(2)均低于对照组(P<0.05);低、中、高黄芪注射液组Schmidt评分、AMS、Hofouaer评分PaCO_(2)依次降低,PaO_(2)依次升高(P<0.05);模型组TNF-α、IL-6高于对照组(P<0.05);低、中、高黄芪注射液组TNF-α、IL-6依次降低(P<0.05);模型组mTOR、p70S6K、p-p70S6K、p-mTOR、4EBP1高于对照组(P<0.05);低、中、高黄芪注射液组mTOR、p70S6K、p-p70S6K、p-mTOR、4EBP1依次降低(P<0.05).结论黄芪注射液可呈剂量依赖性改善AHNP血气指标、炎症反应、胰腺与肺组织病理状态,其机制可能是通过调控mTOR/p70S6K信号通路实现的,抑制mTOR/p70S6K信号通路可能为AHNP肺损伤的治疗提供了一个新思路.
