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  • 林沁1*, 邹忠东2,项协隆1,韦永光1,郑丰1 .罗格列酮对大鼠腹膜透析相关性腹膜纤维化的影响[J].第二军医大学学报,2011,32(2):144-149    [点击复制]
  • LIN Qin1*,ZOU Zhong-dong2 , XIANG Xie-long1,WEI Yong-guang1, ZHENG Feng1 .Influence of rosiglitazone on peritoneal fibrosis induced by peritoneal dialysate in rats[J].Acad J Sec Mil Med Univ,2011,32(2):144-149   [点击复制]
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罗格列酮对大鼠腹膜透析相关性腹膜纤维化的影响
林沁1*,邹忠东2,项协隆1,韦永光1,郑丰1
0
(1. 南京军区福州总医院肾内科,福州 350025; 2. 南京军区福州总医院普通外科,福州 350025)
摘要:
\[摘要\]目的观察罗格列酮(rosiglitazone, RGZ)对腹膜透析所致腹膜纤维化的影响。方法50只SD大鼠随机分为6组: 空白对照组(n=5)、生理盐水(NS)组、模型组、二甲亚砜(DMSO)组、低浓度RGZ组、高浓度RGZ组(后5组n=9)。除空白对照组外其余大鼠均置入腹透管,除空白组和NS组外其余组均采用高糖腹膜透析液+红霉素制作慢性腹膜透析无菌性腹膜纤维化的大鼠模型。DMSO组、低浓度RGZ组、高浓度RGZ组分别采用DMSO、1.5 mg/kg RGZ、15 mg/kg RGZ治疗。透析5周后行1 h腹膜平衡试验,检测血糖及血脂,计算超滤量(UF)、初始腹透液与透出液葡萄糖比值(D1/D0)、透出液与血浆尿素氮比值(D/Purea);处死大鼠,取壁层腹膜行H-E及Masson染色,观察腹膜形态改变,半定量计算腹膜单位面积血管数及炎症细胞数;免疫组化检测腹膜转化生长因子(TGF)-β1和α-平滑肌肌动蛋白(α-SMA)的表达情况。结果与空白对照组相比,模型组和DMSO组间皮下基质增厚,血管增生及炎症细胞浸润增加(P<0.05);TGF-β1、α-SMA表达水平增高(P<0.05);RGZ能改善上述病理改变,下调TGF-β1、α-SMA表达(P<0.05);与空白对照组比较,NS组、模型组、DMSO组、低浓度RGZ组及高浓度RGZ组的超滤量和D1/D0减少,D/Purea增加(P<0.05),其中以DMSO组及模型组改变最为显著。两种剂量RGZ间差异无统计学意义(P>0.05)。结论在大鼠腹膜透析模型中加用罗格列酮能有效保护腹膜功能,抑制腹膜纤维化。
关键词:  罗格列酮  腹膜纤维化  腹膜透析
DOI:10.3724/SP.J.1008.2011.0144
投稿时间:2010-11-26修订日期:2011-01-15
基金项目:福建省科技厅重点资助项目(2008Y0085).
Influence of rosiglitazone on peritoneal fibrosis induced by peritoneal dialysate in rats
LIN Qin1*,ZOU Zhong-dong2 , XIANG Xie-long1,WEI Yong-guang1, ZHENG Feng1
(1. Department of Nephrology, Fuzhou General Hospital, PLA Nanjing Military Area Command, Fuzhou 350025, Fujian, China; 2. Department of General Surgery, Fuzhou General Hospital, PLA Nanjing Military Area Command, Fuzhou 350025, Fujian, China)
Abstract:
\[Abstract\]ObjectiveTo investigate the effect of rosiglitazone (RGZ) in prevention of peritoneal fibrosis induced by peritoneal dialysis in rats.MethodsFifty SD rats were randomly divided into six groups: control group (n=5), normal saline(NS) group(n=9), model group (n=9), dimethyl sulfoxide(DMSO) group(n=9) , low-dose RGZ group (n=9) , and high-dose RGZ group (n=9). Peritoneal catheters were implanted in the last five groups, and peritoneal fibrosis models were induced in the last four groups by high-glucose peritoneal dialysate and erythromycin with rats. Animals in the low-dose RGZ and high-dose RGZ groups were treated with 1.5 mg/kg RGZ and 15 mg/kg RGZ, respectively. The one hour peritoneal equilibration test was performed and the plasma glucose and serum lipids were estimated five weeks after dialysis. The ultrafiltration volume (UF), dialysate-to-plasma urea ratio (D/Purea), and glucose reabsorption (D1/D0) were calculated. The visceral peritoneum tissues of rats were stained with hematoxylin-eosin(H-E) and Masson trichrome staining to observe the changes of peritoneal morphology. Blood vessels and leukocytes of peritoneum were quantified as n/mm2 within the histological sections with H-E staining. The expression of TGF-β1 and α-SMA in the parietal peritoneum was detected by immunohistochemistry assay. ResultsCompared with the control group, the numbers of peritoneal vessels, leukocytes, peritoneal thickness, and the expressions of TGF-β1 and α-SMA were significantly higher in the model group and DMSO group(P<0.05). Administration of RGZ improved the above changes and significantly decreased the expression of TGF-β1 and α-SMA in the model and DMSO groups (P<0.05). Compared with the control group, the UF and D1/D0 were significantly lower and D/Purea was significantly higher in the rest five groups (P<0.05), and there were no significant differences between the low-dose RGZ group and the high-dose RGZ group(P>0.05). ConclusionAdministration of rosiglitazone can effectively protect the ultrofiltration function of peritoneum during peritoneal dialysis and delay the progression of peritoneal fibrosis.
Key words:  rosiglitazone  peritoneal fibrosis  peritoneal dialysis