前列腺素E1脂微球载体制剂对大鼠慢性肾衰竭模型结缔组织生长因子的影响

目的观察前列腺素E1脂微球载体制剂（Lipo-PGE1）对慢性肾衰竭大鼠结缔组织生长因子（CTGF）的影响，探讨该药对慢性肾衰竭的作用机制。方法使用Lipo-PGE1干预5／6肾切除大鼠慢性肾衰竭模型，8周后检测大鼠尿蛋白、肾功能、残肾病理改变，测定组织内CTGF的表达，观察Lipo-PGE1对上述指标的影响。结果与5／6肾切除组比较，Lipo-PGE1治疗组大鼠尿蛋白下降，肾功能明显改善，残肾组织肾小球硬化指数及肾小管-间质病变减轻，肾组织内结缔组织生长因子表达减少。结论Lipo-PGE1可能通过减少肾脏CTGF的表达起到对慢性肾衰竭肾脏的保护作用。     

复方二黄制剂对肾大部切除大鼠肾脏保护作用的疗效观察

目的观察复方二黄制剂对5／6肾切除大鼠慢性肾衰竭的防治作用。方法采用5／6肾切除模型，分为假手术组、肾大部切除组、尿毒清组、复方二黄制剂高剂量组、复方二黄制剂低剂量组，分别灌胃给药共8周。在灌胃前、灌胃后第4周和第8周时将每组大鼠称重，第8周留取24h尿液后处死大鼠，取血，离心取上清，留取肾组织。分别测定尿量、肾重，检测24h尿蛋白、血肌酐（SCr）、尿素氮（BUN），进行统计学分析。结果肾大部切除后，大鼠逐渐出现肾衰竭，复方二黄制剂能使肾衰竭大鼠的体重、肾重／体重比、24h尿蛋白、SCr、BUN有不同程度的改善。结论复方二黄制剂对肾大部切除大鼠的慢性肾衰竭有一定的防治作用。     

虫草制剂对延缓慢性肾衰竭进展的实验研究

目的：为观察中药治疗慢性肾衰竭(CRF)的疗效。方法：采用5／6肾切除大鼠CRF模型，对肾衰大鼠用中药治疗后的肾功能等血液生化指标及残余肾组织病理情况进行了检查。结果：发现中药可降低CRF大鼠的死亡率，降低血Scr和BUN水平，具有明显的延缓CRF进展的作用。在肾组织病理学改变上，中药能延缓肾小球硬化的进展。结论：中药能有效控制慢性肾衰竭的进展。     

重组肝再生增强因子对5/6肾切除大鼠模型肾性贫血的影响

目的：探讨重组人肝再生增强因子（rhALR）对5/6肾切除所致慢性肾衰竭大鼠肾性贫血的影响。方法：将雄性SD大鼠随机分为假手术组、对照组及rhALR组。对照组及rhALR组大鼠行5/6肾切除,术后12周慢性肾衰竭大鼠模型成功,以rhALR对rhALR组大鼠进行治疗,用药1周,于用药结束后24 h比较各组大鼠血常规、血清尿素氮（BUN）、肌酐（Scr）、血清铁、血清促红细胞生成素（EPO）等各项指标。结果：rhALR能升高5/6肾切除肾衰竭大鼠血红蛋白（Hb）、红细胞计数（RBC）、红细胞压积（HCT）、EPO水平,降低肾衰竭大鼠血中Scr及BUN水平。与对照组相比差异有统计学意义。结论：rhALR可有效改善5/6肾切除所致慢性肾衰竭肾性贫血,升高血中Hb、RBC、HCT、EPO水平,并对肾功能有保护作用。     

肾衰保肾胶囊对5/6肾切除大鼠CytC和Fas表达的影响

目的 观察肾衰保肾胶囊对5/6肾切除大鼠CytC蛋白和Fas蛋白表达的影响.方法 采用5/6肾切除致慢性肾衰竭大鼠模型,将实验分3组：假手术组、模型组（5/6肾切除组）、治疗组[5/6肾切除＋肾衰保肾胶囊（0.648 g·kg-1·d-1）].观察实验大鼠治疗前后的一般状态、肾组织的病理改变;采用免疫组织化学法分别检测肾组织中的CytC蛋白和Fas蛋白表达情况.结果 肾衰保肾胶囊能够明显改善大鼠的症状和体征,降低实验大鼠肾组织中的CytC蛋白和Fas蛋白表达,与对照组比较差异有统计学意义.结论 肾衰保肾胶囊对残肾组织的功能和形态有保护作用,能通过Fas、CytC两条凋亡途径减少肾实质细胞凋亡,延缓慢性肾衰竭的进展.     

肾安提取液对5／6肾切除大鼠肾功能的影响

目的探讨肾安提取液对5／6肾切除大鼠肾功能的影响。方法采用5／6肾切除法制作慢性肾衰竭（CRF）大鼠模型，随机分为7组：正常组、假手术组、模型组、肾安2g／kg组、肾安4g／kg组、肾安8g／kg组及阳性药物尿毒清3．6g／kg对照组，给药疗程2个月。大鼠存活率、体重、血尿素氮（BUN）、血肌酐（SCr）为观察指标。结果给药后2个月，肾安提取液三个剂量组BUN和SCr均明显降低；在降低BUN方面，肾安高剂量组明显优于尿毒清组。结论肾安提取液能降低5／6肾切除大鼠BUN、延缓肾功能。     

肾疏宁对体外培养大鼠腹膜间皮细胞AQP1表达的影响

目的：探讨肾疏宁对体外培养大鼠腹膜间皮细胞水通道蛋白1表达的影响。方法：原代培养大鼠腹膜间皮细胞、鉴定后传至第3代后分为5组：空白血清组、1.5%腹膜透析液组、4.25%腹膜透析液组、1.5%腹膜透析液＋肾疏宁含药血清组、4.25%腹膜透析液＋肾疏宁含药血清组。分别采用ELISA酶联免疫法、荧光定量PCR检测水通道蛋白1的表达。结果：1.5%PDS组、4.25%PDS组、1.5PDS%＋肾疏宁含药血清组、4.25%PDS＋肾疏宁含药血清组各组均与空白血清组比较AQP1表达指数均增高（P〈0.05）。结论：证明肾疏宁含药血清有上调体外培养大鼠腹膜间皮细胞上水通道蛋白1的表达的作用。     

羟苯磺酸钙对5／6肾切除大鼠肾脏微血管的保护机制

目的探讨羟苯磺酸钙对5／6肾切除大鼠肾脏微血管的保护作用及其机制。方法复制5／6肾切除大鼠模型，设5／6肾切除模型组和羟苯磺酸钙干预组，在二次手术后第1、2、4、8、12周观察各组大鼠肾功能及残肾组织病理改变。采用免疫组化观察肾脏Ang-1和CD31表达的变化，RT-PCR观察肾脏Ang-1 mRNA的表达并行相关性分析。结果与同时点模型组比较，羟苯磺酸钙干预组大鼠尿蛋白减少、肾功能改善、残肾组织病理改变明显减轻。自第2周开始Ang-1 mRNA及蛋白表达水平升高，其后期的下调趋势变缓、CD31表达增强、肾脏微血管病变显著改善。结论羟苯磺酸钙可能通过增强Ang-1早期的上调幅度并延缓后期的下调来改善5／6。肾切除大鼠肾脏的微血管病变，从而保护肾脏。     

地塞米松在防治腹膜通透性增高中的作用

目的探讨腹膜透析过程中地塞米松对腹膜表面层、间皮细胞形态和腹膜功能的影响.方法24只SD雄性大鼠随机分为4组.第1组大鼠不接受任何注射即行腹膜动力学实验;第2组以4.25%的高糖透析液透析;第3组(地米1组)腹腔内注射4.25%的透析液并加入地塞米松(剂量为0.1 mg/kg),每天1次,连续7d;第4组(地米2组)腹腔内连续注射透析液2周,第1周为普通4.25%透析液,第2周始用上述剂量地塞米松的透析液继续透析1周.以上各组在停止透析48 h后行腹膜动力学实验.然后取前腹壁组织行光镜及电镜检查.结果腹腔注射4.25%的透析液7 d后,腹膜功能呈高通透性,腹膜表面层明显变薄及疏松,腹膜组织呈明显慢性纤维化改变.使用了加入地塞米松透析液的两组动物其腹膜表面层、间皮细胞形态和腹膜功能与对照组比较无显著差异.结论腹腔注射地塞米松对腹膜表面层、间皮细胞形态有很好的保护作用,明显改善大鼠高通透腹膜的转运功能.     

腹膜透析液生物相容性与腹膜间皮细胞

腹膜间皮细胞是腹腔最大的细胞群落,有着十分重要的生理功能。腹膜透析液具有生物不相容性,它通过ＰＨ值,缓冲剂、渗透压、葡萄糖及其降解产物等对间皮细胞及腹膜产生损害,从而影响腹腔局部防御功能并导致腹膜结构的改变。了解各种腹膜透析液生物不相容性的机理,对于改善透析液、保护长期透析时间皮细胞及腹膜功能具有十分重要的意义。     

Regeneration of peritoneal mesothelium in a rat model of peritoneal fibrosis

BACKGROUND: Patients on long-term peritoneal dialysis develop progressive peritoneal fibrosis and loss of mesothelial layer. Regeneration of the mesothelium has been reported in the normal peritoneum but not the fibrotic peritoneum. Moreover, the origin of the regenerated mesothelial cells remains obscure. The aim of this study was to investigate mesothelial regeneration in fibrotic peritoneum induced by chlorhexidine gluconate. METHODS: Peritoneal fibrosis was induced by injection of CG into the peritoneal cavity of Wistar rats. After injection, the abdomen was opened, and the parietal fibrotic peritoneum with mesothelial cells was stripped from the abdominal wall, and then the abdominal incision was closed. Rats were sacrificed, and peritoneal tissues were dissected out at 0, 1, 3, 5, or 7 days after the stripping procedure. RESULTS: Spindle-shaped cells with microvilli appeared on the surface of stripped peritoneum at day 3 after denudation. Immunohistochemistry identified staining for vimentin, a marker of mesoderm cells, in the spindle-shaped cells at days 3, 5, and 7. Expression of alpha-SMA was observed in the same cells at days 3 and 5, but not 7. Expression of cytokeratin and HBME-1, markers for mesothelial cells, in these cells was delayed until day 7. CONCLUSIONS: Mesothelium can regenerate on the fibrotic peritoneum. The regenerated mesothelial cells seem to originate from vimentin-positive mesenchymal cells.     

Myofibroblast transdifferentiation of mesothelial cells is mediated by RAGE and contributes to peritoneal fibrosis in uraemia.

BACKGROUND: Uraemia is associated with fibrosis of the peritoneal membrane, even prior to the start of peritoneal dialysis. Increased carbonyl stress and the resultant formation of advanced glycation end-products (AGEs) are potentially involved. The interaction of AGEs with their cell surface receptor for AGE (RAGE) induces sustained cellular activation, including the production of the fibrogenic growth factor-beta (TGF-beta). TGF-beta is pivotal in the process of epithelial-to-mesenchymal transition with the acquisition of myofibroblast characteristics. We investigated whether antagonism of RAGE prevents uraemia-induced peritoneal fibrosis. In addition, we examined whether myofibroblast transdifferentiation of mesothelial cells contributes to peritoneal fibrosis in uraemia. METHODS: Uraemia was induced in rats by subtotal nephrectomy. Uraemic and age-matched sham-operated rats were treated for 6 weeks with neutralizing monoclonal anti-RAGE antibodies or placebo. Expression of AGE, RAGE, cytokeratin and alpha-smooth muscle actin was evaluated using immunohistochemistry. TGF-beta expression was examined with immunostaining and western blotting, and Snail expression with western blotting. Fibrosis was quantified with a picro-sirius red staining and measurement of the hydroxyproline content of the tissue. RESULTS: Uraemia resulted in the accumulation of AGE, up-regulation of RAGE and TGF-beta and the development of interstitial fibrosis and vascular sclerosis in the peritoneal membrane. Prominent myofibroblast transdifferentiation of mesothelial cells was identified by colocalization of cytokeratin and alpha-smooth muscle actin in submesothelial and interstitial fibrotic tissue. The antagonism of RAGE prevented the up-regulation of TGF-beta, epithelial-to-mesenchymal transition of mesothelial cells and fibrosis in uraemia. CONCLUSION: The ligand engagement of RAGE and the subsequent up-regulation of TGF-beta induces peritoneal fibrosis in chronic uraemia. The process may be mediated by the conversion of mesothelial cells into myofibroblasts.     

扶肾颗粒对腹膜透析相关性腹膜纤维化的影响及其作用机制的实验研究

目的:通过对腹膜透析大鼠进行干预,观察扶肾颗粒对腹膜纤维化相关细胞因子的影响及其作用机制探讨。方法:SPF级健康雄性SD大鼠75只,体重180～200g,适应性饲养1周后,依大鼠体重分层,随机分为:正常对照组(A组,n=15),无任何处理,腹腔注射生理盐水,100ml.kg-1.d-1,连续4周;肾衰5/6切除+1.5%PD组(B组,n=15);肾衰5/6切除+1.5%PD+扶肾颗粒组(C组,n=15);肾衰5/6切除+4.25%PD组(D组,n=15);肾衰5/6切除+4.25%PD+扶肾颗粒组(E组,n=15),除A组外,各组均制成肾衰模型,其中B、C组予腹腔注射1.5%LPDS,100ml.kg-1.d-1,连续4周;D、E组予腹腔注射4.25%LPDS,100ml.kg-1.d-1,连续4周,自透析开始,对C组和E组予灌服扶肾颗粒,以200gSD大鼠计算,灌胃剂量1.8ml/d。其余各组予灌服2ml生理盐水,共灌服4周。观察各组实验动物的大体状态、体重变化、腹膜滤过功能及血清纤维化调控因子表达变化。结果:在治疗4周后,除正常对照组(A组)外,其余各组均体现为负超滤,但是,同浓度透析治疗组中,应用扶肾颗粒干预组其超滤情况明显优于未应用扶肾颗粒组(P<0.05),其作用显著,同时,葡萄糖转运量方面亦体现为相似结果。与正常对照组比较(A组),其余各模型组相关促纤维化因子表达水平均明显升高(P<0.01)。TGF-β1方面,D组的表达水平明显较其他各组升高(P<0.05)。CTGF及IL-6方面,结果与TGF-β1相似。VEGF方面,E组较D组明显降低(P<0.05)。随着透析治疗的进行,HGF与BMP-7表达水平均反应性升高,各模型组二者水平均较正常对照组明显升高(P<0.01)。HGF方面,C组较B组明显升高(P<0.01)。BMP-7方面,E组较D组明显升高(P<0.05)。结论:扶肾颗粒可减轻腹透大鼠的肾功能损伤,保护残余肾功能,改善腹透大鼠的超滤量及葡萄糖转运量,抑制促纤维化因子TGF-β1、CTGF、IL-6、CTGF等表达,调高抗纤维化因子HGF、BMP-7的表达,进而起到抑制腹膜透析相关腹膜纤维化的发生,改善腹膜透析效能。     

Hepatocyte growth factor prevents peritoneal fibrosis in an animal model of encapsulating peritoneal sclerosis

BACKGROUND: Ultrafiltration failure associated with peritoneal fibrosis can lead patients to discontinue continuous ambulatory peritoneal dialysis (CAPD). It has been reported that the reciprocal imbalance between transforming growth factor-beta1 (TGF-beta1) and hepatocyte growth factor (HGF) is closely involved in the progression of tissue fibrosis. We previously showed that exogenous HGF restores the growth of human peritoneal mesothelial cells suppressed by a high concentration of D-glucose or TGF-beta1. In this study, we examined whether constitutive exposure to HGF prevents peritoneal fibrosis in an animal model of encapsulating peritoneal sclerosis (EPS). METHODS: To establish the model, a daily intraperitoneal injection of 0.1% chlorhexidine gluconate was given to male Wister rats for 35 days. Rat peritoneal mesothelial cells (RPMCs) transfected with full-length human HGF cDNA in an expression vector (pUCSRalpha/HGF) were injected into the peritoneal cavity of the rats. Thereafter, pathological changes to the peritoneal membrane were observed, and the effect on peritoneal ultrafiltration volume was examined. RESULTS: In the model, microscopic examination revealed a progressive thickening of the submesothelial layer, and an increase in the number of capillary vessels. Peritoneal ultrafiltration volume was decreased. Interestingly, the pathological changes to the peritoneal membrane were reversed by the intraperitoneal injection of pUCSRalpha/HGF-transfected RPMCs. Furthermore, peritoneal ultrafiltration volume was increased. CONCLUSIONS: The constitutive production of HGF by UCSRalpha/HGF-transfected RPMCs can improve peritoneal fibrosis resulting in an increase in peritoneal ultrafiltration volume. This approach may have clinical application.     

参脉注射液对心脏瓣膜置换术的心肌保护作用

目的探讨参脉注射液(SMI)在心脏瓣膜置换术中对心肌缺血-再灌注损伤的保护作用。方法将40例心脏瓣膜置换术患者随机均分为参脉组(SM组)和对照组(C组),SM组在心肺转流(CPB)前静脉给予SMI,C组用等量生理盐水。分别于术前、术中、术后多时点采血,比较两组心肌磷酸激酶(CK)、磷酸激酶同工酶(CK-MB)、肌钙蛋白I(cTnI)、丙二醛(MDA)、超氧化物歧化酶(SOD)水平;记录两组患者的手术时间、主动脉阻断时间及术中、术后各时点血管活性药物的用量,观察主动脉开放后心脏自动复跳率、室性心律失常发生率。结果SM组血清CK、CK-MB、cTnI、MDA等指标均低于C组(P<0.05),而两组SOD活性均降低,但SM组明显高于C组(P<0.05)。SM组室性心律失常发生率、除颤次数及血管活性药物的用量明显低于C组(P<0.01)。结论SMI对心脏瓣膜置换术患者心肌缺血-再灌注损伤具有明显保护作用。     

Apparent successful mesothelial cell transplantation hampered by peritoneal activation

BACKGROUND: Mesothelial cell transplantation has been suggested to improve mesothelial repair after surgery, recurrent peritonitis and peritoneal dialysis. METHODS: In this study we evaluated mesothelial cell transplantation during the resolution phase of experimentally thioglycollate-induced peritonitis in rats. To this end 4 x 10(6) DiO-labeled autologous mesothelial cells were transplanted 1 week after peritonitis induction. Peritoneal inflammation and permeability characteristics were evaluated after another week. RESULTS: Mesothelial cell transplantation after peritonitis resulted in incorporation of these cells in the parietal mesothelial lining, leading to an acute transient submesothelial thickening which was not seen in transplanted animals without prior peritonitis induction. Long-term functioning of these repopulated mesothelial cells leaded to peritoneal activation as evidenced by a approximately twofold increase in peritoneal lymphocytes (P < 0.01) and omental mast cell counts (P < 0.05), accompanied by the induction of inflammation markers monocyte chemoattractant protein-1 (MCP-1) (P < 0.01) and hyaluronan (P < 0.01) in the transplanted peritonitis group, but not in rats with peritonitis without mesothelial cell transplantation or in control rats without mesothelial cell transplantation (all four parameters P < 0.01). In addition, trapping of transplanted mesothelial cells in the milky spots of omental tissue and lymphatic stomata of the diaphragm both in control and thioglycollate rats seems to increase microvascular permeability, reflected by apparent increased diffusion rates of small solutes and proteins. CONCLUSION: Altogether, our data underscore the importance of controlling peritoneal (patho)physiology and function in mesothelial transplantation protocols.     

上调Smad7表达对腹膜纤维化大鼠腹膜间皮细胞转分化的影响

目的探讨上调TGF-β抑制性信号蛋白Smad7表达对大鼠腹膜纤维化模型腹膜间皮细胞转分化的影响。方法30只160～170 g SD雄性大鼠.随机分为4组：正常对照组（n=6）;腹膜纤维化模型组（n=12）：予腹腔注射4.25%腹膜透析液与脂多糖;空载体组（n=6）：模型成功后转染pTRE与pEFpurop-Tet-on质粒;Smad7治疗组（n=6）：模型成功后转染pTRE- m2 Smad7与pEFpurop-Tet-on质粒。第14、28天杀检大鼠,取脏层腹膜组织,用RT-PCR方法检测TGF-B1、α-SMA、E-钙黏蛋白（E-cadherin）基因的表达;用Western杂交或间接免疫荧光的方法检测TGF-β1、Smad7、磷酸化（p）-Smad2/3、α-SMA、E-cadherin的表达。结果与正常对照组比较,模型组TGF-β1、p-Smad2/3及α-SMA的表达显著上调（p〈0.01）;E-cadherin的表达显著下调（P〈0.01）。与模型组、空载体组比较,Smad7治疗组p-Smad2/3及α-SMA表达水平显著下调（P〈0.01）;E-cadherin的表达显著上调,但仍低于正常对照组（P〈0.05）。结论Smad7可通过抑制受体调控信号蛋白Smad2/3的活化,阻止高糖透析液及脂多糖介导的腹膜间皮细胞转分化,从而防止腹膜纤维化的发生和发展。     

Adenoviral-mediated gene expression of hepatocyte growth factor prevents postoperative peritoneal adhesion in a rat model

BACKGROUND: Mesothelial cell proliferation and migration play important roles in reducing formation of postoperative peritoneal adhesions. Hepatocyte growth factor (HGF) is a multifunctional cytokine that stimulates proliferation and migration of various cell types, including mesothelial cells. METHODS: We investigated the effect of adenovirus-mediated HGF gene expression on the proliferation and migration of mesothelial cells and evaluated its preventive effects on postoperative formation of peritoneal adhesions. Rat mesothelial cells were isolated and characterized by expression of cytokeratin and vimentin. RESULTS: Immunohistochemical staining showed that these cells expressed c-Met, the receptor for HGF. Adenoviral-mediated HGF gene transfer into mesothelial cells resulted in high expression of HGF and enhanced migration. To evaluate the preventive effects of adenoviral-mediated HGF gene transfer on the formation of postoperative peritoneal adhesion, we employed a rat model of cecum abrasion-induced adhesion formation in which 80% of the rats developed postoperative peritoneal adhesions. Local application of recombinant adenovirus carrying the HGF gene reduced adhesion formation in 16 of 20 control rats compared with 7 of 20 treated rats in this model. CONCLUSIONS: These results suggest that adenoviral-mediated HGF gene transfer may be a novel strategy for preventing postoperative peritoneal adhesions.     

上调Smad7表达对大鼠腹膜纤维化模型腹膜间皮细胞转分化的影响

目的 探讨上调Smad7表达对腹膜纤维化大鼠模型腹膜间皮细胞转分化的影响，为进一步研究防止腹膜纤维化的措施提供依据。 方法 将24只体重180~200 g SD雄性大鼠随机分为4组:A组(6只):正常对照组；B组(6只):腹膜纤维化模型组，每日按100 ml/kg腹腔注射4.25%透析液，并于造模后第8、10、12、22、24、26天按0.6 mg/kg腹腔注射脂多糖(LPS)；C组(6只):空白载体组，在建立模型的第1、14天转染空白载体和pEF purop-Tet-on质粒；D组(6只):Smad7转染组，在建立模型第1、14天转染Smad7和pEF purop-Tet-on质粒。各组均在每日饮水中加入强力霉素(200 mg/L)诱导基因表达。所有动物于实验第28天杀检，取脏层腹膜组织行光镜及电镜检查。用RT-PCR、间接免疫荧光和Western印迹方法检测α-SMA、E-钙黏蛋白(cadherin)、Smad7、磷酸化(P)-Smad2/3 mRNA和蛋白表达。 结果 与正常对照组比较，腹膜纤维化模型组和空白载体组p-Smad2/3蛋白水平显著升高，α-SMA mRNA和蛋白表达上调，但E-cadherin mRNA和蛋白水平明显下调。电镜结果显示，腹膜纤维化模型组和空白载体组腹膜间皮细胞微绒毛脱落，基底膜断裂，并向间皮下组织迁徙，胞浆中有密体、密斑和肌丝出现。与上述2组比较，Smad7基因转染组Smad7蛋白表达明显增加，p-Smad2/3蛋白水平明显下调，α-SMA mRNA和蛋白水平也明显降低，而E-cadherin mRNA和蛋白水平无明显变化。电镜结果显示，Smad7基因转染组腹膜间皮细胞微绒毛明显增多，细胞连接和基底膜趋于完整。 结论 基因转染上调Smad7表达可通过部分抑制TGF-β受体调控信号通路(Smad2/3)，抑制腹膜间皮细胞向肌成纤维细胞的转分化。     

Zymosan induces nitric oxide production by peritoneal mesothelial cells

Introduction: The production of nitric oxide is an important peritoneal defense mechanism. We have evaluated the effect of various putative stimulants on nitric oxide production by peritoneal mesothelial cells. Methods: Wistar rats were randomized to either a control group or a peritonitis group (5 mg zymosan intraperitoneally). Groups of five animals were sacrificed at 4, 18, 24, 48 and 96 h after the induction of peritonitis and their peritoneal fluid was harvested for assay. Cultures of peritoneal mesothelial cells were stimulated with lipopolysaccharide, myeloperoxidase, TNFα, zymosan, peritoneal fluid from a control animal and peritoneal fluid from a peritonitis animal. Supernatants were collected after incubation for 4, 24 and 48 h for assay. The assay for nitric oxide was based upon the nitrite content of the samples. Results: The intraperitoneal administration of zymosan was associated with an increased production of nitric oxide (NO) when compared with control animals (P < 0.01). In cultures of peritoneal mesothelial cells, zymosan, but not the other putative stimulants, was associated with a marked output of nitric oxide (P < 0.001). Conclusion: Zymosan has a direct effect on peritoneal mesothelial cells, which are able to generate nitric oxide in the absence of co‐stimulatory molecules. This suggests that it may be possible to use some form of external stimulation to up‐regulate the NO response by peritoneal mesothelial cells.