INTRODUCTIONMultiple organ dysfunction syndrome (MODS) isthought to be a frequent consequence of sepsis[1-3].Despite substantial advances in our knowledge and understanding of the basic pathophysiologic mechanisms[4-7...INTRODUCTIONMultiple organ dysfunction syndrome (MODS) isthought to be a frequent consequence of sepsis[1-3].Despite substantial advances in our knowledge and understanding of the basic pathophysiologic mechanisms[4-7], in critically ill patients infections and sepsis are still associated with a high mortality[8,9].展开更多
Cardiac dysfunction, a common consequence of sepsis, is the major contribution to morbidity and mortality in patients. Sodium tanshinone IIA sulfonate(STS) is a water-soluble derivative of Tanshinone IIA(TA), a main a...Cardiac dysfunction, a common consequence of sepsis, is the major contribution to morbidity and mortality in patients. Sodium tanshinone IIA sulfonate(STS) is a water-soluble derivative of Tanshinone IIA(TA), a main active component of Salvia miltiorrhiza Bunge, which has been widely used in China for the treatment of cardiovascular and cerebral system diseases. In the present study, the effect of STS on sepsis-induced cardiac dysfunction was investigated and its effect on survival rate of rats with sepsis was also evaluated. STS treatment could significantly decrease the serum levels of C-reactive protein(CRP), procalcitonin(PCT), cardiac troponin Ⅰ(cTn-Ⅰ), cardiac troponin T(cTn-T), and brain natriuretic peptide(BNP) in cecal ligation and puncture(CLP)-induced) septic rats and improve left ventricular function, particularly at 48 and 72 h after CLP. As the pathogenesis of septic myocardial dysfunction is attributable to dysregulated systemic inflammatory responses, several key cytokines, including tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-10(IL-10) and high mobility group protein B1(HMGB1), were detected to reveal the possible mechanism of attenuation of septic myocardial dysfunction after being treated by STS. Our study showed that STS, especially at a high dose(15 mg×kg–1), could efficiently suppress inflammatory responses in myocardium and reduce myocardial necrosis through markedly reducing production of myocardial TNF-α, IL-6 and HMGB1. STS significantly improved the 18-day survival rate of rats with sepsis from 0% to 30%(P < 0.05). Therefore, STS could suppress inflammatory responses and improve left ventricular function in rats with sepsis, suggesting that it may be developed for the treatment of sepsis.展开更多
目的:探讨脓毒症并发急性肾损伤时大鼠肾脏结构和功能的变化,以及核因子-κB(NF-κB)在肾脏组织中的表达。方法:雄性SD大鼠36只,随机分为假手术组(Sham组)和盲肠结扎穿孔组(CLP组),各18只。CLP组大鼠采用盲肠结扎穿孔法建立脓毒症动物模...目的:探讨脓毒症并发急性肾损伤时大鼠肾脏结构和功能的变化,以及核因子-κB(NF-κB)在肾脏组织中的表达。方法:雄性SD大鼠36只,随机分为假手术组(Sham组)和盲肠结扎穿孔组(CLP组),各18只。CLP组大鼠采用盲肠结扎穿孔法建立脓毒症动物模型,Sham组除不结扎穿孔盲肠外,其余处理同脓毒症组。分别于造模后6、12和24 h观察各组心率(HR)、平均动脉压(MAP)、血清肌酐(Cr)、尿素氮(BUN)的变化及肾脏组织的改变;免疫组织化学法检测肾脏组织中NF-κB的表达情况。结果:与相同时间点Sham组比较,CLP组6～12 h HR、MAP明显升高(P<0.01和P<0.05),24 h MAP降低(P<0.01)。与相同时间点Sham组比较,CLP组6～24 h BUN均升高(P<0.05～P<0.01),24 h Cr明显升高(P<0.01)。CLP各组大鼠肾小体中血管球淤血、皱缩,肾小囊腔扩大,且随病程延长,淤血、皱缩的血管球增多,且伴有肾小管上皮细胞肿胀和坏死。Sham组NF-κB位于细胞质中,着色浅;CLP组NF-κB移位进入细胞核,着色加深。结论:随脓毒症病程的延长,大鼠肾脏结构和功能损伤加重。NF-κB在细胞核内的高表达提示NF-κB的活化可能是促进肾脏结构和功能损伤的重要因素。展开更多
目的观察脓毒症状态下大鼠心肌细胞凋亡对心肌力学的影响。方法 60只体重230-280 g的Wistar大鼠随机分成对照组（n=30）、脓毒症组（n=30）。脓毒症组采用盲肠结扎穿孔法（CLP）制作脓毒症模型,对照组采取开关腹法（不进行盲肠结扎穿孔...目的观察脓毒症状态下大鼠心肌细胞凋亡对心肌力学的影响。方法 60只体重230-280 g的Wistar大鼠随机分成对照组（n=30）、脓毒症组（n=30）。脓毒症组采用盲肠结扎穿孔法（CLP）制作脓毒症模型,对照组采取开关腹法（不进行盲肠结扎穿孔）。两组动物均经右颈内动脉插管监测术后24 h的血流动力学指标,检测左室心肌细胞凋亡率,两组间采用独立样本t检验进行心功能及细胞凋亡率比较,并就心室收缩峰压与心肌细胞凋亡率进行相关性分析。结果脓毒症组的收缩压（SBP,95±5 mm Hg）,舒张压（DBP,62±10 mm Hg）,平均动脉压（MAP,73±7 mm Hg）、左心室收缩峰压（LVSP,83±5 mm Hg）、左室压力上升最大速率（＋dp/dtmax,2 784±40 mm Hg）明显低于对照组（130±7mm Hg,70±11 mm Hg,89±8 mm Hg,137±8 mm Hg,4 928±137 mm Hg）,左心室舒张末压（LVEDP,-1±2 mm Hg）及左心室压力下降最大速率（-dp/dtmax,-2 386±210 mm Hg）明显高于对照组（-11±2 mm Hg,-4 814±344 mm Hg）,差异有统计学意义（P〈0.01）。脓毒症组大鼠的心肌细胞凋亡率（8.10%±0.58%）明显高于对照组（0.51%±0.02%）,差异有统计学意义（P〈0.01）。脓毒症组大鼠心肌细胞凋亡率增加,左心室收缩峰压降低,呈负相关性（r=-0.68）。结论脓毒症时心肌力学明显下降,心肌细胞凋亡率增加,脓毒症24 h心功能与心肌细胞凋亡存在负相关。展开更多
基金Supported by the National Natural Science Foundation of China, No. 39870796
文摘INTRODUCTIONMultiple organ dysfunction syndrome (MODS) isthought to be a frequent consequence of sepsis[1-3].Despite substantial advances in our knowledge and understanding of the basic pathophysiologic mechanisms[4-7], in critically ill patients infections and sepsis are still associated with a high mortality[8,9].
文摘Cardiac dysfunction, a common consequence of sepsis, is the major contribution to morbidity and mortality in patients. Sodium tanshinone IIA sulfonate(STS) is a water-soluble derivative of Tanshinone IIA(TA), a main active component of Salvia miltiorrhiza Bunge, which has been widely used in China for the treatment of cardiovascular and cerebral system diseases. In the present study, the effect of STS on sepsis-induced cardiac dysfunction was investigated and its effect on survival rate of rats with sepsis was also evaluated. STS treatment could significantly decrease the serum levels of C-reactive protein(CRP), procalcitonin(PCT), cardiac troponin Ⅰ(cTn-Ⅰ), cardiac troponin T(cTn-T), and brain natriuretic peptide(BNP) in cecal ligation and puncture(CLP)-induced) septic rats and improve left ventricular function, particularly at 48 and 72 h after CLP. As the pathogenesis of septic myocardial dysfunction is attributable to dysregulated systemic inflammatory responses, several key cytokines, including tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-10(IL-10) and high mobility group protein B1(HMGB1), were detected to reveal the possible mechanism of attenuation of septic myocardial dysfunction after being treated by STS. Our study showed that STS, especially at a high dose(15 mg×kg–1), could efficiently suppress inflammatory responses in myocardium and reduce myocardial necrosis through markedly reducing production of myocardial TNF-α, IL-6 and HMGB1. STS significantly improved the 18-day survival rate of rats with sepsis from 0% to 30%(P < 0.05). Therefore, STS could suppress inflammatory responses and improve left ventricular function in rats with sepsis, suggesting that it may be developed for the treatment of sepsis.
文摘目的:探讨脓毒症并发急性肾损伤时大鼠肾脏结构和功能的变化,以及核因子-κB(NF-κB)在肾脏组织中的表达。方法:雄性SD大鼠36只,随机分为假手术组(Sham组)和盲肠结扎穿孔组(CLP组),各18只。CLP组大鼠采用盲肠结扎穿孔法建立脓毒症动物模型,Sham组除不结扎穿孔盲肠外,其余处理同脓毒症组。分别于造模后6、12和24 h观察各组心率(HR)、平均动脉压(MAP)、血清肌酐(Cr)、尿素氮(BUN)的变化及肾脏组织的改变;免疫组织化学法检测肾脏组织中NF-κB的表达情况。结果:与相同时间点Sham组比较,CLP组6～12 h HR、MAP明显升高(P<0.01和P<0.05),24 h MAP降低(P<0.01)。与相同时间点Sham组比较,CLP组6～24 h BUN均升高(P<0.05～P<0.01),24 h Cr明显升高(P<0.01)。CLP各组大鼠肾小体中血管球淤血、皱缩,肾小囊腔扩大,且随病程延长,淤血、皱缩的血管球增多,且伴有肾小管上皮细胞肿胀和坏死。Sham组NF-κB位于细胞质中,着色浅;CLP组NF-κB移位进入细胞核,着色加深。结论:随脓毒症病程的延长,大鼠肾脏结构和功能损伤加重。NF-κB在细胞核内的高表达提示NF-κB的活化可能是促进肾脏结构和功能损伤的重要因素。
文摘目的观察脓毒症状态下大鼠心肌细胞凋亡对心肌力学的影响。方法 60只体重230-280 g的Wistar大鼠随机分成对照组（n=30）、脓毒症组（n=30）。脓毒症组采用盲肠结扎穿孔法（CLP）制作脓毒症模型,对照组采取开关腹法（不进行盲肠结扎穿孔）。两组动物均经右颈内动脉插管监测术后24 h的血流动力学指标,检测左室心肌细胞凋亡率,两组间采用独立样本t检验进行心功能及细胞凋亡率比较,并就心室收缩峰压与心肌细胞凋亡率进行相关性分析。结果脓毒症组的收缩压（SBP,95±5 mm Hg）,舒张压（DBP,62±10 mm Hg）,平均动脉压（MAP,73±7 mm Hg）、左心室收缩峰压（LVSP,83±5 mm Hg）、左室压力上升最大速率（＋dp/dtmax,2 784±40 mm Hg）明显低于对照组（130±7mm Hg,70±11 mm Hg,89±8 mm Hg,137±8 mm Hg,4 928±137 mm Hg）,左心室舒张末压（LVEDP,-1±2 mm Hg）及左心室压力下降最大速率（-dp/dtmax,-2 386±210 mm Hg）明显高于对照组（-11±2 mm Hg,-4 814±344 mm Hg）,差异有统计学意义（P〈0.01）。脓毒症组大鼠的心肌细胞凋亡率（8.10%±0.58%）明显高于对照组（0.51%±0.02%）,差异有统计学意义（P〈0.01）。脓毒症组大鼠心肌细胞凋亡率增加,左心室收缩峰压降低,呈负相关性（r=-0.68）。结论脓毒症时心肌力学明显下降,心肌细胞凋亡率增加,脓毒症24 h心功能与心肌细胞凋亡存在负相关。
