干扰素-α对高糖环境下腹膜间皮细胞合成细胞外基质的影响

目的通过研究干扰素-α(IFN-α)对高糖环境下腹膜间皮细胞(HPMCs)分泌纤维连结蛋白(FN)、转化生长因子-β1(TGF-β1)、基质金属蛋白酶2(MMP-2)的影响,探讨其对腹膜透析相关性腹膜纤维化的防治意义。方法收集行不卧床持续腹膜透析(CAPD)尿毒症患者腹膜透出液中的腹膜间皮细胞,进行原代培养,传代细胞用于实验。设实验组和对照组,实验组加2.5%的葡萄糖及不同剂量的干扰素,培养不同时间分别收集上清液,用ELISA法检测其中的FN、TGF-β1、MMP-2含量,并进行统计学分析。结果各加2.5%葡萄糖的实验组FN含量及TGF-β1含量均高于对照组,差异具有显著性(P<0.05);加干扰素的实验组FN及TGF-β1含量均低于不加干扰素的实验组,差异具有浓度依赖性,浓度为1000u时达到高峰;MMP-2含量:对照组与实验组间无显著性差异。结论高浓度葡萄糖可促进腹膜间皮细胞表达FN、TGF-β1,但对MMP-2含量无显著影响。而干扰素对FN、TGF-β1具有相反的作用,提示其可能减少CAPD时细胞外基质的堆积,对预防、延缓腹膜纤维化有一定意义。     

肝素在高糖影响大鼠腹膜间皮细胞的增殖及其表达白细胞介素-1中的作用

目的 初步观察肝素在高糖影响大鼠腹膜间皮细胞(Rat pcritoneal mesothelial cells，BPMC)细胞增殖及其表达白细胞介素—1(Interleukin-1,IL-1)中的作用，从而为持续性非卧床腹膜透析(Continuous ambulatory pcritoncal dialysis，CAPD)中肝素的临床应用打下一定的理论基础。方法 建立BPMC的体外培养；并用四四氮唑蓝(MTT)细胞增殖实验和酶联免疫吸附方法(ELISA)，来分析肝素对高糖(3．86％葡萄糖)影响RPMC增殖及其分泌IL—1的作用。结果 3．86％葡萄糖能显抑制BPMC的增殖，而1．25U／ml肝素能部分逆转高糖对RPMC增殖的抑制作用(P＜0．01)；3．86％葡萄糖能显增加BPMC表达IL—1β，而1．25U／ml肝素能部分减少高糖增加BPMC表达IL-1β的作用(P＜0．01)。结论 本结果提示，肝素可能通过逆转高糖对BPMC的增殖抑制作用及减少高糖增加RPMC表达促炎细胞因子IL—1的作用，而延续CAPD相关性腹膜纤维化的发生，最终有益于CAPD进行。     

虫草肾茶胶囊对人肾小球系膜细胞分泌转化生长因子β1及细胞外基质的影响

目的研究虫草肾茶胶囊对培养在高糖条件下系膜细胞(HMC)分泌转化生长因子β1(TGF-β1)及细胞外基质(ECM)的影响,探讨其在糖尿病肾病(DN)防治中的意义。方法应用血清药理学方法,制备虫草肾茶胶囊及福辛普利药物血清,利用酶联免疫吸附试验(ELISA)测定经体外培养的HMC在各种处理因素的作用下上清液中TGF-β1、纤维连接蛋白和层粘连蛋白的表达情况,并以福辛普利为对照。结果高糖能明显促进HMC分泌TGF-β1、纤维连接蛋白和层粘连蛋白(P<0.05或P<0.01)。而虫草肾茶胶囊能抑制HMC分泌TGF-β1、纤维连接蛋白和层粘连蛋白,并呈一定量效关系(P<0.05或P<0.01),且某些方面明显优于福辛普利。结论高糖可促进HMC TGF-β1及ECM分泌,虫草肾茶胶囊能明显抑制高糖条件下HMC分泌TGF-β1及ECM,有助于预防糖尿病肾小球硬化的发生和发展。     

血红素加氧酶-1对高糖诱导大鼠腹膜间皮细胞转化生长因子β_1和纤维连接蛋白表达的影响

目的研究血红素加氧酶-1(HO-1)对高糖作用下体外培养的大鼠腹膜间皮细胞(RPMC)转化生长因子β1(TGF-β1)和纤维连接蛋白(FN)表达的影响。方法将原代培养的第3代RPMC随机分为对照组、高糖组、钴原卟啉(CoPP)+高糖组和CoPP组。同步培养72h后,以反转录聚合酶链反应(RT-PCR)法检测各组细胞TGF-β1和FNmRNA表达情况;酶联免疫吸附法(ELISA)检测细胞上清液中TGF-β1和FN的蛋白质水平。结果高糖组、CoPP+高糖组和CoPP组的HO-1mRNA及蛋白表达水平均显著高于对照组,其中CoPP+高糖组显著高于高糖组;高糖组和CoPP+高糖组的FNmRNA及蛋白表达水平显著高于对照组及CoPP组;高糖组、CoPP+高糖组TGF-β1mRNA及蛋白表达水平显著高于对照组及CoPP组,其中CoPP+高糖组显著低于高糖组。结论 HO-1可抑制高糖诱导的RPMCTGF-β1和FN的表达,具有抗腹膜纤维化的作用。     

蛋白激酶C对高糖作用下腹膜间皮细胞葡萄糖转运蛋白1调节作用

目的观察蛋白激酶C(PKC)对高糖作用下体外培养的大鼠腹膜间皮细胞(PMCs)胞膜上葡萄糖转运蛋白1(GLUT1)表达的调节,以探讨长期腹膜透析时如何避免腹膜损伤、改善腹膜透析疗效。方法胰酶消化法提取雄性Wistar大鼠的PMCs细胞进行培养,分别加入不同浓度葡萄糖及PKC抑制剂Go6976,间接免疫荧光法检测PMCs上GLUT1表达,流式细胞仪检测作用前后细胞膜上GLUT1量的改变,生化分析仪检测培养液内葡萄糖浓度的变化。结果高糖可增加细胞膜上GLUT1的表达,同时伴有PMCs对葡萄糖的转运增加(P0.05)。Go6976明显抑制了高糖对GLUT1的诱导,且葡萄糖的转运亦下降。结论葡萄糖以浓度依赖方式上调PMCs细胞膜上GLUT1的蛋白表达,同时伴有PMCs对葡萄糖转运的增加。PKC通路在其中发挥重要作用,应用PKC抑制剂可拮抗高糖对GLUT1表达的诱导作用。     

糖皮质激素对人腹膜间皮细胞分泌细胞外基质的影响

目的探讨糖皮质激素对人腹膜间皮细胞分泌细胞外基质的影响。方法采用胰蛋白酶消化法从人腹膜组织中分离间皮细胞,建立稳定的体外培养模型。将第三代细胞转板,至细胞融合后,将其分为:①对照组(F12);②2.5%葡萄糖组(F12 葡萄糖2.5%);③LPS组(F12 LPS10mg/L);④2.5%葡萄糖加DXM组(DXM为3种不同的浓度,依次为10nmol/L、100nmol/L、1000nmol/L);⑤LPS加DXM组(DXM为三种不同的浓度,依次为10nmol/L、100nmol/L、1000nmol/L);所有分组均培养24h后收集细胞上清液,低温离心(1000r/m)5min后,采用酶联免疫吸附法检测上清液中纤维连接蛋白(FN)和纤溶酶原抑制剂(PAI-1)的含量。结果①腹膜间皮细胞在2.5%葡萄糖和10mg/LLPS刺激下分泌FN及PAI-1明显增加,与对照组比较差异有显著性意义(P<0.01);10mg/LLPS组分泌FN及PAI-1较2.5%葡萄糖组分泌高,差异有显著性意义(P<0.01);②腹膜间皮细胞在2.5%葡萄糖加入不同浓度的DXM(10nmol/L、100nmol/L、1000nmol/L)干预后,24h内分泌FN及PAI-1较2.5%葡萄糖组减少,差异有显著性(P<0.05);③腹膜间皮细胞在LPS加入不同浓度的DXM(10nmol/L、100nmol/L、1000nmol/L)干预后,24h内分泌FN及PAI-1较LPS组减少,差异有显著性意义(P<0.05)。     

pcDU6质粒载体介导的TGFβ1shRNA及pcDNA3.1介导的TGF-β1反义RNA抑制人腹膜间皮细胞TGFβ1的表达及细胞外基质的分泌

目的研究转化生长因子β1(TGF-β1)短发夹RNA(short hairpin RNA,shRNA)和TGF-β1反义RNA对体外培养的人腹膜间皮细胞(HPMC)TGF-β1表达及细胞外基质分泌的影响.方法利用带有U6启动子的pcDNA3.1(-)载体(命名为pcDU6)构建TGF-β1短发夹RNA的产生质粒,用pcDNA3.1(-)载体构建反义TGF-β1基因真核表达载体,采用胰蛋白酶消化法从人大网膜组织中分离间皮细胞,建立稳定的体外培养模型.用脂质体转染表达转化生长因子β1shRNA的pcDU6载体质粒和表达反义TGF-β1RNA的pcDNA3.1(-)的载体质粒人高糖(4.25%D-葡萄糖)和细菌脂多糖(LPS)刺激下人腹膜间皮细胞.采用逆转录多聚酶链式反应(RT-PCR)半定量分析HPMC中TGF-β1mRNA的表达以及纤维连接蛋白(FN)、Ⅰ型纤溶酶原激活物抑制剂(PAI-1)和胶原Ⅰ(ColⅠ)的mRNA表达.采用双抗夹心法酶联免疫吸附实验检测HPMC培养液中TGF-β1蛋白质水平.结果HPMC在高糖(4.25%D-葡萄糖)和细菌脂多糖(LPS)的刺激下可明显上调TGF-β1的表达(P＜0.01),TGF-β1反义RNA转染HPMC后,与对照组相比,转染24小时后,FN、ColⅠ、PAI-1 mR-NA分别下调17.0%、26.0%、9.6%(P＜0.05).pcDU6载体质粒介导的转化生长因子β1shRNA干扰组较Gs LPS组及pcDU6空载体组明显下调TGF-β1的表达(P＜0.01),pcDNA3.1(-)的载体质粒介导的反义RNA组与pcDU6空载体组比较差异无显著性(P＞0.05),pcDU6载体质粒介导的转化生长因子β1shRNA干扰组较pcDNA3.1(-)的载体质粒介导的反义RNA组明显下调TGF-β1的表达(P＜0.01).结论pcDU6载体质粒介导的转化生长因子β1shRNA能够明显抑制在高糖(4.25%D-葡萄糖)和细菌脂多糖(LPS)的刺激下的HPMC转化生长因子β1的基因表达,可能为临床防治长期腹膜透析患者的腹膜纤维化提供一种较为有效的方法.     

普伐他汀对高糖培养的肾小球系膜细胞增殖和细胞外基质积聚的影响

目的:探讨普伐他汀对高糖培养的肾小球系膜细胞(MC)增殖和细胞外基质(ECM)积聚的影响。方法:大鼠MC分别培养在低糖组、高糖组及普伐他汀组。CCK-8测定MC增殖,ELISA法检测细胞培养上清液Ⅳ型胶原(Col-Ⅳ)、纤维连接蛋白(FN)、转化生长因子-β1(TGF-β1)、基质金属蛋白酶组织抑制因子-1(TIMP-1)的分泌情况,明胶酶谱法检测基质金属蛋白酶-2(MMP-2)和基质金属蛋白酶-9(MMP-9)的活性,RT-PCR法检测结缔组织生长因子(CTGF)mRNA的表达。结果:与低糖组相比,高糖能促进Col-Ⅳ、FN合成,抑制MMP-2、MMP-9活性,增加TIMP-1、TGF-β1、CTGF的分泌,而普伐他汀能一定程度上逆转上述现象。结论:普伐他汀能抑制高糖环境下的MC增殖,并通过抑制ECM的合成、促进ECM的降解减少ECM积聚,机制可能与抑制TGF-β1、CTGF有关。     

普伐他汀对高糖培养的肾小球系膜细胞增殖和细胞外基质积聚的影响

摘要 目的：探讨普伐他汀对高糖培养的肾小球系膜细胞(MC)增殖和细胞外基质（ECM）积聚的影响。方法：大鼠MC分别培养在低糖组, 高糖组及普伐他汀组。CCK-8测定MC增殖，ELISA法检测细胞培养上清液Ⅳ型胶原(Col-Ⅳ)、纤维连接蛋白(FN)、转化生长因子-β1 (TGF-β1)、基质金属蛋白酶组织抑制因子-1 (TIMP-1)的分泌情况；明胶酶谱法检测基质金属蛋白酶-2（MMP-2）和基质金属蛋白酶-9（MMP-9）的活性，RT-PCR 法检测结缔组织生长因子(CTGF)mRNA的表达。结果：与低糖组相比，高糖能促进Col-Ⅳ、FN合成，抑制MMP-2 、MMP-9活性，增加TIMP-1、TGF-β1、CTGF的分泌，而普伐他汀能一定程度上逆转上述现象。结论：普伐他汀能抑制高糖环境下的MC增殖，并通过抑制 ECM 的合成、促进ECM的降解减少ECM积聚，机制可能与抑制TGF-β1、CTGF有关。     

血红素加氧酶-1对高糖诱导大鼠腹膜间皮细胞转化生长因子β1和纤维连接蛋白表达的影响

目的研究血红素加氧酶-1（HO-1）对高糖作用下体外培养的大鼠腹膜间皮细胞（RPMC）转化生长因子β1（TGF-β1）和纤维连接蛋白（FN）表达的影响。方法将原代培养的第3代RPMC随机分为对照组、高糖组、钴原卟啉（CoPP）＋高糖组和CoPP组。同步培养72h后,以反转录聚合酶链反应（RT-PCR）法检测各组细胞TGF-β1和FNmRNA表达情况;酶联免疫吸附法（ELISA）检测细胞上清液中TGF-β1和FN的蛋白质水平。结果高糖组、CoPP＋高糖组和CoPP组的HO-1mRNA及蛋白表达水平均显著高于对照组,其中CoPP＋高糖组显著高于高糖组;高糖组和CoPP＋高糖组的FNmRNA及蛋白表达水平显著高于对照组及CoPP组;高糖组、CoPP＋高糖组TGF-β1mRNA及蛋白表达水平显著高于对照组及CoPP组,其中CoPP＋高糖组显著低于高糖组。结论 HO-1可抑制高糖诱导的RPMCTGF-β1和FN的表达,具有抗腹膜纤维化的作用。     

Increased expression of basement membrane components in human endothelial cells cultured in high glucose.

Although the degree of hyperglycemia is a powerful and independent risk factor for diabetic microvascular disease, it has not been established if and how high glucose per se can induce the typical lesions of microangiopathy. We have investigated in human vascular endothelial cells the expression of messenger RNA (mRNA) for collagen type IV and fibronectin, the two glycoproteins characteristically increased in diabetic basement membranes. In 12 confluent primary cultures exposed for 11 +/- 1 d (mean +/- SD) to 30 mM glucose and exhibiting cell number and thymidine incorporation similar to control cultures, the levels of collagen IV and fibronectin mRNA were, respectively, 238 +/- 140 and 221 +/- 231 percent of control (P less than 0.01). The effects of high glucose were selective (the levels of collagen I and c-myc mRNA remained unchanged), independent of the proliferative activity of the cultures and of the plating substratum, and maintained throughout multiple passages. However, several days of exposure to high glucose were required before their appearance. These observations establish that high glucose is a perturbation sufficient to mimic the effects of diabetes on the regulation of basement membrane components and propose that modifications in gene expression may pertain to the chain of events leading to diabetic angiopathy.     

Insulin-like growth factor I mediates selective anabolic effects of parathyroid hormone in bone cultures.

PTH was studied for its effects on bone formation in cultured rat calvariae. 0.01-10 nM PTH stimulated [3H]thymidine incorporation into DNA by up to 4.8-fold. Although continuous treatment with PTH for 24-72 h inhibited [3H]proline incorporation into collagen, transient (24 h) treatment enhanced [3H]proline incorporation into collagen 24-48 h after the hormone was removed. The collagen stimulated by PTH was type I and the effect was observed in the periosteum-free bone and was not blocked by hydroxyurea. Furthermore, treatment with 1-100 nM PTH for 24 h increased insulin-like growth factor (IGF) I concentrations by two to fourfold, and an IGF I antibody prevented the PTH stimulation of collagen synthesis, but not its mitogenic effect. In conclusion, continuous treatment with PTH inhibits calvarial collagen, whereas transient treatment stimulates collagen synthesis, and the stimulatory effect is mediated by local production of IGF I.     

Effect of insulinlike growth factor I on DNA and protein synthesis in cultured rat calvaria.

Insulinlike growth Factor I (IGF I), a growth hormone-dependent peptide or somatomedin, was studied for its effects on bone formation by examining the synthesis of DNA, collagen, and noncollagen protein in cultures of 21-d fetal rat calvaria. IGF I caused a dose-dependent stimulation of the incorporation of [3H]thymidine into DNA at concentrations of 0.1--100 nM; the effect appeared after 6 h, was maximal at 12 h, and was sustained for 96 h. IGF I also increased the bone DNA content, IGF I at 0.1--3 nM had a small stimulatory effect on the incorporation of [3H]proline into collagenase-digestible protein (CDP) whereas 30 nM IGF I caused a two- to threefold increment and had a maximal effect. A smaller effect on the labeling of noncollagen protein (NCP) was also observed. The effect of CDP and NCP appeared and was maximal after 12 h and was sustained for 96 h. IGF I increased the total collagen content of bones. The IGF I stimulatory effect on the incorporation of [3H]thymidine was seen in both the periosteum and periosteum-free calvarium, whereas that on the labeling of CDP was seen only in the central, osteoblastic-rich, non-periosteal bone. Histological sections showed a 10-fold increase in the mitotic index after Colcemid arrest in IGF I-treated bones, the mitoses were equally distributed in the periosteum and central portions of the calvarium. Insulin had a stimulatory effect on the incorporation of [3H]proline into CDP and NCP and 1 nM--1 microM similar to the effect of IGF I. In contrast, high insulin concentrations (0.1 and 1 microM) were required to increase the incorporation of [3H]thymidine, and insulin did not affect DNA content. Cortisol decreased the stimulatory effect of IGF I on DNA labeling but greatly enhanced the stimulatory effect of IGF I on the incorporation of [3H]proline into CDP. Triiodothyronine and parathyroid hormone increased the incorporation of [3H]thymidine and were additive to IGF I. Triiodothyronine did not affect the labeling of CDP, but parathyroid hormone inhibited it and opposed the effect of IGF I. These studies indicate that IGF I stimulates bone DNA, collagen, and NCP synthesis in vitro. IGF I and insulin have similar effects on bone collagen synthesis but IGF I stimulates the synthesis of DNA at physiological concentrations, and insulin does not.     

Effects of basic fibroblast growth factor on bone formation in vitro.

Basic fibroblast growth factor (bFGF) was studied for its effects on bone formation in cultured rat calvariae. bFGF at 0.1-100 ng/ml stimulated [3H]thymidine incorporation into DNA by up to 4.4-fold. bFGF also increased the number of colcemid-induced metaphase arrested cells and the DNA content. Transient (24 h) treatment with bFGF enhanced [3H]-proline incorporation into collagen 24-48 h after the factor was removed; this effect was DNA synthesis dependent and blocked by hydroxyurea. The collagen stimulated by bFGF was type I, and this effect was observed primarily in the periosteum-free bone. In contrast, continuous treatment with bFGF for 24-96 h inhibited [3H]proline incorporation into type I collagen. bFGF did not alter collagen degradation. In conclusion, bFGF stimulates calvarial DNA synthesis, which causes an increased number of collagen-synthesizing cells, but bFGF has a direct inhibitory effect on collagen synthesis.     

Effects of endothelial cell growth factor on bone remodelling in vitro.

Endothelial cell growth factor (ECGF) alpha was studied for its effects on bone formation in cultured fetal rat calvariae and on bone resorption in cultured fetal rat long bones. ECGF at 0.1-100 ng/ml stimulated [3H]thymidine incorporation into DNA, an effect enhanced by heparin. Treatment with ECGF for 24 h decreased the incorporation of [3H]proline into collagen but treatment for 48-96 h increased collagen and noncollagen protein synthesis, an effect that was concomitant with an increase in DNA content. ECGF did not alter collagen degradation in calvariae or 45Ca release from long bones, which indicated it had no effect on bone resorption. Although ECGF increased prostaglandin E2 concentrations, its effect on DNA synthesis was not prostaglandin-mediated. In conclusion, ECGF stimulates calvarial DNA synthesis, which is an effect that results in a generalized increase in protein synthesis, but ECGF has no effect on matrix degradation or bone resorption.     

Interleukin-1beta stimulates the production of extracellular matrix in cultured human peritoneal mesothelial cells.

OBJECTIVE: To investigate the effect of interleukin-1beta (IL-1beta) on the production of extracellular matrix in cultured human peritoneal mesothelial cells (HPMCs). DESIGN: Cultured HPMCs were treated with or without IL-1beta. Cell morphology was observed. The expression of fibronectin, alpha1(I) procollagen, and transforming growth factor-beta1 (TGFbeta1) mRNAs was measured by Northern blot analysis. The cell surface expression of fibronectin and type I collagen was evaluated by immunofluorescent staining. Fibronectin and type I collagen in culture supernatant were measured by inhibition ELISA. RESULTS: Interleukin-1beta induced morphologic change in HPMCs from a cuboidal epithelioid shape into an elongated fibroblastoid shape.The elongated cells were positive for cytokeratin although they had a fibroblastoid appearance. Treatment of HPMCs with IL-1beta resulted in increased expression of both fibronectin and alpha1(I) pro-collagen mRNA in dose- and time-dependent manners. Immunofluorescent staining showed strong and diffuse cytoplasmic expression of fibronectin and type I collagen in the cells treated with IL-1beta, whereas only weak perinuclear cytoplasmic staining was noted in the cells on media alone. The concentrations of secreted fibronectin and type I collagen in culture supernatant were significantly higher in the cells treated with IL-1beta than in the control cells. IL-1beta also stimulated the expression of TGFbeta1 mRNA. However, IL-1beta-induced fibronectin mRNA expression was only partially blocked by neutralizing anti-TGFbeta antibody. CONCLUSION: Interleukin-1beta stimulated the production of extracellular matrix in cultured HPMCs along with the induction of morphologic changes.This may play a role in the development of peritoneal fibrosis caused by peritonitis or bioincompatible dialysate in continuous ambulatory peritoneal dialysis patients.     

Hepatic and peripheral insulin action in chronic renal failure before and during continuous ambulatory peritoneal dialysis

1. A three-step hyperinsulinaemic euglycaemic clamp was performed in six uraemic patients before dialysis and after 3 months of treatment with continuous ambulatory peritoneal dialysis, and in seven matched normal control subjects. Glucose turnover was assessed basally and during the clamp using [3-3H]glucose as a tracer. 2. The glucose infusion rate required to maintain euglycaemia was insignificantly higher in normal subjects compared with undialysed uraemic subjects at each insulin infusion rate. 3. The isotopically assessed total glucose turnover was also similar in normal and uraemic subjects. Basal hepatic glucose output was again similar in uraemic and control subjects and output was suppressed to a similar degree at each insulin infusion rate. 4. After treatment with continuous ambulatory peritoneal dialysis, the glucose infusion rate and the total glucose turnover during the clamp rose significantly at all three insulin concentrations (P less than 0.05), but remained insignificantly different from normal control values. Hepatic glucose output was unchanged. 5. Peripheral insulin action was improved during continuous ambulatory peritoneal dialysis, but hepatic insulin action was unchanged.     

中药复方861对肝星状细胞的增殖和胶原合成的影响

目的 研究中药复方861对血管紧张素Ⅱ(AngⅡ)引起的肝星状细胞增殖、细胞内钙浓度及胶原合成的影响。方法 体外实验对象为肝星状细胞系(HSC—T6)。细胞增殖采用甲基-^3H胸腺嘧啶核苷(-^3H—TdR)掺人法，细胞内钙浓度测定用Fluo-3／AM(乙酰氧甲基酯)标记后共聚焦显微镜下测定荧光光密度值。培养上清液中I型胶原(CoL—I)用酶联免疫吸附(ELISA)法测定，Ⅲ型前胶原肽(PⅢP)的浓度用放免法检测。HSC-T6细胞CoL—Ⅰ及Ⅲ型胶原(CoI一Ⅲ)mRNA的水平用RT—PCR方法检测。结果 AngⅡ可促进HSC-T6细胞的增殖和细胞内钙浓度的增加，复方861可阻断这些变化。复方861也可降低HSC—T6细胞CoL—Ⅰ及PⅢP的分泌和CoL—Ⅰ及CoL—Ⅲ mRNA的水平。结论 复方861通过作用于血管紧张素Ⅱ1型受体(AT1R)抑制肝星状细胞的增殖及胶原蛋白的合成，这可能是其抗纤维化的机理之一。     

Peritoneal transport of glucose in rat.

OBJECTIVE: To evaluate the convective transport characteristics of glucose and the effect of high glucose and insulin during experimental peritoneal dialysis in rat. METHODS: Male Sprague-Dawley rats weighing 300-400 g were used in this study. Mannitol (5%) was used as osmotic agent. Glucose was added to dialysis solution to yield a concentration of 100 mg/dL (group 1) or 300 mg/dL (group 2). Mannitol solution (5%) containing the same concentration of electrolytes and lactate but without glucose was used as control (group 3). In group 2, blood sugar was maintained at approximately 300 mg/dL by continuous intravenous infusion of 25% glucose solution and 0.9% NaCl solution. A 2-hour dwell study was performed with 30 mL of test solutions. Intraperitoneal volume was calculated by volume marker (18.5 kBq of 131I-human radioiodinated serum albumin, RISA) dilution with corrections made for the elimination of RISA from the peritoneal cavity (K(E)) and sample volume. The diffusive mass transport coefficient (K(BD)) and sieving coefficient (S(BRF)) were calculated by using the Babb-Randerson-Farrell model. S was also calculated directly by using isocratic methods (S(I)).The peritoneal fluid absorption rate (K(E)) was taken into account for the calculation of S(I). RESULTS: Intraperitoneal volume was significantly higher in group 2 compared with groups 1 and 3. Peritoneal fluid absorption rate, K(E), was similar in all three groups. S(BRF) and S(I) for glucose were significantly lower in group 2 compared with groups 1 and 3. S(BRF) for glucose in group 2 was below zero and S(I) near zero. K(BD) for glucose was significantly higher in group 2 than in groups 1 and 3. Plasma and dialysate concentrations of insulin increased during the initial hour and then decreased to the baseline value in groups 1 and 3, while in group 2 it continuously increased. CONCLUSION: Significantly lower sieving coefficients for glucose in the high glucose and high insulin group suggest that transport mechanisms other than simple passive transport are involved in peritoneal glucose transport, and that high glucose per se and/or high insulin may be important factors that determine glucose transport characteristics.