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目的探讨血必净注射液对脓毒症所致急性肾损伤(AKI)的内皮及细胞外基质的保护作用,为临床提供新的治疗思路。方法健康雄性SD大鼠30只,随机分为假手术组(Sham组)、生理盐水组(NS组)和血必净组(XBJ组),每组10只。采用盲肠结扎穿孔(CLP)法制作脓毒症动物模型,术后6h处死动物并取肾组织,光镜下观察组织形态学改变,透射电镜下观察组织超微结构改变,经RT-PCR半定量检测肾组织中ET-1、i NOS、MMP-9和TIMP-1的m RNA表达水平。结果光镜下,肾组织HE染色显示XBJ组肾小球、肾小管组织形态改变较NS组轻;透射电镜下,XBJ组肾小球、近曲小管超微结构改变较NS组轻。与Sham组比,NS组肾组织中ET-1、i NOS、MMP-9和TIMP-1的m RNA表达水平均明显升高(P<0.05,P<0.01);XBJ组肾组织中ET-1、i NOS、MMP-9和TIMP-1的表达水平明显低于NS组(P<0.05),但仍高于Sham组(P<0.01)。结论血必净注射液可通过降低肾组织ET-1、i NOS、MMP-9和TIMP-1的m RNA表达水平,保护内皮及细胞外基质稳定性,从而减轻脓毒症大鼠肾损伤。

目的探讨血必净注射液对脓毒症所致急性肾损伤（AKI）的内皮及细胞外基质的保护作用,为临床提供新的治疗思路。方法健康雄性SD大鼠30只,随机分为假手术组（Sham组）、生理盐水组（NS组）和血必净组（XBJ组）,每组10只。采用盲肠结扎穿孔（CLP）法制作脓毒症动物模型,术后6h处死动物并取肾组织,光镜下观察组织形态学改变,透射电镜下观察组织超微结构改变,经RT-PCR半定量检测肾组织中ET-1、i NOS、MMP-9和TIMP-1的m RNA表达水平。结果光镜下,肾组织HE染色显示XBJ组肾小球、肾小管组织形态改变较NS组轻;透射电镜下,XBJ组肾小球、近曲小管超微结构改变较NS组轻。与Sham组比,NS组肾组织中ET-1、i NOS、MMP-9和TIMP-1的m RNA表达水平均明显升高（P〈0.05,P〈0.01）;XBJ组肾组织中ET-1、i NOS、MMP-9和TIMP-1的表达水平明显低于NS组（P〈0.05）,但仍高于Sham组（P〈0.01）。结论血必净注射液可通过降低肾组织ET-1、i NOS、MMP-9和TIMP-1的m RNA表达水平,保护内皮及细胞外基质稳定性,从而减轻脓毒症大鼠肾损伤。

目的研究氨基胍对兔骨关节炎软骨细胞凋亡的影响。方法将32只兔子随机分组,正常组未采取任何处理,氨基胍组及模型组行右后肢伸直位管型石膏固定造模,氨基胍组腹腔内注射100 mg/（kg.d）氨基胍硫酸盐溶液,模型组每天腹腔内注射相同体积的生理盐水。分别于4周和8周处死动物,留取标本观察软骨大体形态,切片HE染色观察镜下形态,免疫组化检测iNOS表达,TUNEL法原位检测凋亡。结果与模型组相比,氨基胍组在大体形态、HE切片镜下形态接近于正常组,组化染色显示iNOS表达阳性细胞数显著减少（P〈0.05）,TUNEL法原位检测显示凋亡阳性细胞数显著减少（P〈0.05）。结论氨基胍能有效减少iNOS表达和软骨细胞的凋亡,延缓OA的病情发展。

目的探讨低频噪音（次声）对大鼠胃组织一氧化氮合酶表达的影响。方法210只SD大鼠，其中140只随机分为8Hz-90dB、8Hz-130dB、16Hz-130dB实验组及对照A组，按组别暴露于上述参数的次声舱中，2h／d；于次声作用1、7、14、21、28d随机取出7只检测其胃组织中诱导型一氧化氮合酶（iNOS）、内皮型一氧化氮合酶（eNOs）的表达。另外70只大鼠随机分为暴露组和对照B组，暴露组作用参数为8Hz-130dB，2h／d，连续暴露14d；于停止次声作用后1、7、14、21、28d随机取出7只进行上述指标检查。结果①8Hz-90dB次声作用14、21d，8Hz-130dB次声作用7、14、21、28d，16Hz-130dB次声作用7、14d，大鼠胃组织iNOS的表达均明显高于对照A组（P〈0．05，P〈0.01），各组均以14d最为明显，且8Hz-130dB组iNOS的表达明显高于其他实验组（P〈0．05，P〈0．01）；②8Hz-130dB次声作用14d停止暴露后胃组织iNOS表达阳性率逐渐下降，但仍高于对照B组（P〈0．05，P〈0．01）；③上述参数的次声作用后胃组织eNOS表达与对照组比较差异无统计学意义。结论①不同频率和强度的低频噪音均可引起大鼠胃组织iNOS表达增加，其表达的水平与作用次声的频率、强度和作用时间有关；②大鼠对次声的多次作用可产生一定适应性，停止次声作用后，胃组织iNOS表达有自我恢复趋势；③同样参数的次声对胃组织eNOS的表达无明显影响。

目的观察中药慈菇消脂丸对大鼠非酒精性脂肪性肝炎（NASH）的防治作用。方法建立非酒精性脂肪性肝炎大鼠模型，随机分为正常组、模型组、慈菇消脂丸高剂量组、慈菇消脂丸低剂量组、东宝肝泰阳性药物对照组，观察肝组织病理形态学的变化，检测肝组织中丙二醛（MDA）、超氧化物歧化酶（SOD）、一氧化氮（NO）的含量。免疫组化技术检测环氧合酶-2（COX-2）及诱导型一氧化氮合酶（iNOS）在肝脏的表达。结果模型组大鼠肝组织出现脂肪变性及不同程度的炎性细胞浸润，镜下可见肝细胞内大量脂滴。与正常组相比较，模型组大鼠肝组织内SOD活性显著降低，MDA、NO含量显著提高，COX-2、iNOS蛋白表达显著提高，差异具有统计学意义；与模型组相比较，中药治疗组大鼠肝组织内SOD活性显著提高，MDA、NO含量显著降低，COX-2、iNOS蛋白表达显著降低，差异具有统计学意义；中药慈菇消脂丸高剂量组作用亦较阳性药物对照组显著。结论慈菇消脂丸对大鼠非酒精性脂肪性肝炎具有明显的防治作用，其作用机制与改善肝组织脂肪变性程度、抑制脂质过氧化、抗炎有关。

目的探讨胃癌中环氧化酶-2(Cox-2)、诱导型一氧化氮合酶(iNOS)的表达及其与胃癌血管生成的关系。方法用免疫组化SP法检测45例胃癌、癌旁组织手术切除标本Cox-2、iNOS和微血管密度(MVD)的表达。结果胃癌组织Cox-2和iNOS的表达率以及MVD均明显高于癌旁组织(77．78％vs．33．33％，68．89％vs5．17．78％，58．13±19．99vs．24．02±10．28，P<0．01，P<0．005，P<0．05)。Cox-2和iNOS均与MVD呈正相关(r=0．63，r=0．54，P<0．05，P<0．05)。Cox-2和iNOS表达有显著相关性(P<0．05)。结论Cox-2和iNOS在胃癌的发生中有协同作用，两者可能共同参与肿瘤血管的形成。

Inflammasomes are multi-protein complexes that trigger the activation of caspase-1 and the maturation of interleukin-1β （IL-1β）, yet the regulation of these complexes remains poorly characterized. Here we show that nitric oxide （NO） inhibited the NLRP3-mediated ASC pyroptosome formation, caspase-1 activation and IL-1β secretion in myeloid cells from both mice and humans. Meanwhile, endogenous NO derived from iNOS （inducible form of NO synthase） also negatively regulated NLRP3 inflammasome activation. Depletion of iNOS resulted in increased accu- mulation of dysfunctional mitochondria in response to LPS and ATP, which was responsible for the increased IL-1β production and caspase-1 activation, iNOS deficiency or pharmacological inhibition of NO production enhanced NL-RP3-dependent cytokine production in vivo, thus increasing mortality from LPS-induced sepsis in mice, which was prevented by NLRP3 deficiency. Our results thus identify NO as a critical negative regulator of the NLRP3 inflam-masome via the stabilization of mitochondria. This study has important implications for the design of new strategies to control NLRP3-related diseases.

Aim： To investigate the mechanisms underlying the protective effects of quercetin-rutinoside （rutin） and its aglycone quercetin against CCl4-induced liver damage in mice. Methods： BALB/cN mice were intraperitoneally administered rutin （10, 50, and 150 mg/kg） or quercetin （50 mg/kg） once daily for 5 consecutive days, followed by the intraperitoneal injection of CCl4 in olive oil （2 mL/kg, 10% v/v）. The animals were sacrificed 24 h later. Blood was collected for measuring the activities of ALT and AST, and the liver was excised for assessing Cu/Zn superoxide dismutase （SOD） activity, GSH and protein concentrations and also for immunoblotting. Portions of the livers were used for histology and immunohistochemistry.Results： Pretreatment with rutin and, to a lesser extent, with quercetin significantly reduced the activity of plasma transaminases and improved the histological signs of acute liver damage in CCl4-intoxicated mice. Quercetin prevented the decrease in Cu/Zn SOD activity in CCl4-intoxicated mice more potently than rutin. However, it was less effective in the suppression of nitrotyrosine formation. Quercetin and, to a lesser extent, rutin attenuated the inflammation in the liver by down-regulating the CCl4-induced activation of nuclear factor-kappa B （NF-κB）, tumor necrosis factor-α （TNF-α） and cyclooxygenase （COX-2）. The expression of inducible nitric oxide synthase （iNOS） was more potently suppressed by rutin than by quercetin. Treatment with both flavonoids significantly increased NF-E2-related factor 2 （Nrf2） and heme oxygenase （HO-1） expression in injured livers, although quercetin was less effective than rutin at an equivalent dose. Quercetin more potently suppressed the expression of transforming growth factor-β1 （TGF-β1） than rutin.Conclusion： Rutin exerts stronger protection against nitrosative stress and hepatocellular damage but has weaker antioxidant and anti-inflammatory activities and antifibrotic potential than quercetin, which may be attributed to the presence of a rutinoside moiety in position 3 of the C ring.

Total joint replacement is a highly successful surgical procedure for treatment of patients with disabling arthritis and joint dysfunction. However, over time, with high levels of activity and usage of the joint, implant wear particles are generated from the articulating surfaces. These wear particles can lead to activation of an inflammatory reaction, and subsequent bone resorption around the implant （periprosthetic osteolysis）. Cells of the monocyte/macrophage lineage orchestrate this chronic inflammatory response, which is dominated by a pro-inflammatory （M 1） macrophage phenotype rather than an anti-inflammatory pro-tissue healing （M2） macrophage phenotype. While it has been shown that interleukin-4 （IL-4） selectively polarizes macrophages towards an M2 anti-inflammatory phenotype which promotes bone healing, rather than inflammation, little is known about the time course in which this occurs or conditions in which repolarization through I L-4 is most effective. The goal of this work was to study the time course of murine macrophage polarization and cytokine release in response to challenge with combinations of polymethyl methacrylate （PMMA） particles, lipopolysaccharide （LPS） and IL-4 in vitro. Treatment of particle-challenged monocyte/macrophages with IL-4 led to an initial suppression of pro-inflammatory cytokines and inducible nitric oxide synthase （iNOS） production and subsequent polarization into an M2 anti-inflammatory phenotype. This result was optimized when IL-4 was delivered before PMMA particle challenge, to an M 1 phenotype rather than to uncommitted （MO） macrophages. The effects of this polarization were sustained over a 5-day time course. Polarization of M1 macrophages into an M2 phenotype may be a strategy to mitigate wear particle associated periprosthetic osteolysis.

Sepsis is a life-threatening health condition that is initially characterized by uncontrolled inflammation, followed by the development of persistent immunosuppression. YCP is a novel α-glucan purified from the mycelium of the marine fungus Phoma herbarum YS4108, which has displayed strong antitumor activity via enhancing host immune responses. In this study, we investigated whether YCP could influence the development of sepsis in a mouse model. Caecal ligation and puncture （CLP）-induced sepsis was established in mice that were treated with YCP （20 mg/kg, ip or iv） 2 h before, 4 and 24 h after the CLP procedure, and then every other day. YCP administration greatly improved the survival rate （from 39% to 72% on d 10 post-CLP） and ameliorated disease symptoms in the septic mice. Furthermore, YCP administration significantly decreased the percentage of myeloid-derived suppressor cells （MDSCs） in the lungs and livers, which were dramatically elevated during sepsis. In cultured BM-derived cells, addition of YCP （30, 100 pg/mL） significantly decreased the expansion of MDSCs; YCP dose-dependently decreased the phosphorylation of STAT3 and increased the expression of interferon regulatory factor-8 （IRF-8）. When BM-derived MDSCs were co-cultured with T cells, YCP dose-dependently increased the production of arginase-1 （Arg-1） and inducible nitric oxide synthase （iNOS）, and activated the NF-KB pathway. In addition, the effects of YCP on MDSCs appeared to be dependent on toll-like receptor （TLR） 4. These results reveal that YCP inhibits the expansion of MDSCs via STAT3 while enhancing their immunosuppressive function, partially through NF-KB. Our findings suggest that YCP protects mice against sepsis by regulating MDSCs. Thus, YCP may be a potential therapeutic agent for sepsis.