Objectives To evaluate the effects of external application of Xiaozhang Tie on ascites and the mechanism related to vascular permeability of peritoneum and liver in cirrhotic mice.Methods Dimethylnitrosamine was injected intraperitoneally for four weeks to induce liver cirrhosis in mice.After ascites were identified by ultrasound, the animals were randomly divided into five groups (n=10 each) : model (untreated control) ;placebo (plaster matrix only control) , low-dose Xiaozhang Tie (0.125 cm2 plaster) ;mid-dose Xiaozhang Tie (0.25 cm2 plaster) ;and high-dose Xiaozhang Tie (0.5 cm2 plaster) .Uninduced mice (n=10) were used as normal controls.Xiaozhang Tie (652.9 mg crude drug/kg weight) was applied by external application to the umbilical once daily for one week.The amount of ascites, abdominal circumference, and body weight were recorded.Inflammation and fibrosis of liver tissue were observed by hemotoxylin-eosin and Sirius rose staining.Serum alanine aminotransferase (ALT) , albumin, total bilirubin (TBil) , and nitric oxide (NO) were tested.Liver expression of vascular endothelial growth factor (VEGF) was assessed by Western blotting.Evans blue (EB) staining in ascites and liver tissue was used to evaluate vascular permeability of peritoneum and liver.Results Before external application, the abdominal circumference and body weight of cirrhotic mice were comparable.After external application, amount of ascites, abdominal circumference, body weight, ascites index, EB in ascites and liver tissue, serum NO, and VEGF protein expression in liver tissue were all higher than in the normal group.The amount of ascites in the placebo group and model group was similar.Compared to the placebo group, the amount of ascites and ascites index were lower in the Xiaozhang Tie mid-dose and high-dose groups.The abdominal circumference and body weight were lower in the high-dose group than in either the placebo or low-dose groups.Three dosages of Xiaozhang Tie did not produce any observable effects on liver function or pathology.Compared to the model group, EB in ascites, serum NO, and VEGF protein expression in liver tissue were obviously decreased in the Xiaozhang Tie mid-dose group.Conclusion Xiaozhang Tie administered as 0.25 cm2 plaster external application may reduce ascites in cirrhotic mice.Furthermore, the mechanism of this effect may involve attenuation of VEGF expression in liver tissue, reduction of the NO level in serum, and resolving the abnormally higher vascular permeability in peritoneum.
[1]范开春, 程留芳.肝硬化腹水发生机制[J].中华肝脏病杂志, 2003, 11 (3) :180.
|
[2]刘成海, 张雅丽, 冯年平, 等.实胀方与虚胀方辨证敷脐对肝硬化腹水的作用[J].中国中西医结合杂志, 2006, 26 (5) :411-414.
|
[3]Xing F, Tan Y, Yan GJ, et al.Effects of Chinese herbal cata-plasm Xiaozhang Tie on cirrhotic ascites[J].J Ethnopharma-col, 2012, 139 (2) :343-349.
|
[4]潘传芳, 张雅丽, 蔡俊萍, 等.肝硬化腹水的敷脐疗法[J].中西医结合肝病杂志, 2004, 14 (2) :126-128.
|
[5]Ala-kokko L, Pihlajaniemi T, Myers JC, et al.Gene expres-sion of type I, III andⅣcollagens in hepatic fibrosis inducedby dimethylnitrosamine in the rat[J].Biochem J, 1987, 244 (1) :75-79.
|
[6]薛立文.艾灸小鼠“神阙”穴对小肠推进功能影响的观察[J].实用预防医学, 2007, 14 (4) :1258-1259.
|
[7]Melgar-Lesmes P, Tugues S, Ros J, et al.Vascular endo-thelial growth factor and angiopoietin-2 play a major role inthe pathogenesis of vascular leakage in cirrhotic rats[J].Gut, 2009, 58 (2) :285-292.
|
[8]童光东, 周大桥, 贺劲松, 等.麝黄膏脐敷治疗肝硬化难治性腹水临床研究[J].中西医结合消化杂志, 2003, 11 (5) :290-292.
|
[9]张萍, 任永申, 付强, 等.软肝消水巴布剂对S180腹水模型小鼠的治疗作用[J].解放军药学学报, 2005, 23 (4) :259-262.
|
[10]Proctor E, Chatamra K.High yield micronodular cirrhosis in therat[J].Gastroenterology, 1982, 83 (6) :1183-1190.
|
[11]Senger DR, Van de Water L, Brown LF, et al.Vascular per-meability factor (VPF, VEGF) in tumor biology[J].CancerMetastasis Rev, 1993, 12 (3-4) :303-324.
|
[12]Toyoak M, Jefrey RH, Marcy Silver BS, et al.Vascular endo-thelia A growth factor/vascular perm eability factor enhancesvascular permeability via Nitric Oxide and prostacydin[J].Cir-culation, 1998, 97 (1) :99-107.
|