Functional and structural alterations of peritoneum and secretion of fibrotic cytokines in rats caused by high glucose peritoneal dialysis solutions.

OBJECTIVE: To determine functional and structural alterations of peritoneum and fibrotic cytokines expression in peritoneal dialysis (PD) rats. METHODS: 28 Sprague-Dawley (S-D) rats were randomly divided into four groups and dialyzed with various solutions daily for four weeks: (1) no solution (CON group), (2) 0.9% Saline solution (NS group), (3) 1.5% Dianeal (LG group), (4) 4.25% Dianeal (HG group). Peritoneal equilibration tests, ultrafiltration function and effluent protein quantification were measured. Peritoneum morphology was studied and immunohistochemistry were performed for detection of transforming growth factor ß1 (TGF-ß1), connective tissue growth factor (CTGF), and fibronectin (FN) proteins. Reverse transcriptional-polymerase chain reaction was used to analyze the expression of TGF-ß1, CTGF mRNA. RESULTS: Administration of 4.25% Dianeal caused functional and structural changes of peritoneum, including protein loss through the transport process, decrease of peritoneal solute transport rate and ultrafiltration capacity. The collagen of peritoneum in the HG group was thicker than the other groups. The levels of CTGF, TGF-ß1, and FN proteins were significantly the highest in the HG group, followed by the LG group. The liner correlation analysis showed positive correlations between the levels of CTGF, TGF-ß1, and FN proteins and the collagen thickness. The expression of TGF-ß1 and CTGF mRNA in the HG group were significantly higher than those in the other groups and were indicated positive correlation. CONCLUSION: Using high glucose peritoneal dialysis solutions in rats may not only lead to processing of peritoneal fibrosis, which is promoted by ectopic expression of TGF-ß1, but also increase the expression of CTGF. CTGF is an important fibrotic media of peritoneal fibrosis in PD rats.

Enhancing effect of ultrasound-mediated microbubble destruction on gene delivery into rat kidney via different administration routes.

OBJECTIVE: To investigate the efficiency of ß-galactosidase gene transfer into rat kidney with ultrasound-mediated microbubble destruction via different injection routes. METHODS: A total of 25 Wistar rats were randomly divided into 5 groups. Four groups received a mixture of optison microbubbles (0.2 mL) and lacz plasmids (25 µg) injection via renal artery, tail vein, anterior tibial muscle and renal parenchyma, respectively. The control group received a mixture of PBS (xx mL) and lacz plasmids (25 µg) via renal artery. Three days after the gene transfer, ultrasound with fixed frequency and power (1 MHz, xxW) was delivered to the kidneys for 3 min. The efficiency of the gene transfer and expression was evaluated on the basis of ß-galactosidase expression. The side effects of this method were evaluated by immunohistological method. RESULTS: ß-galactosidase expression could be observed only in tubules but not in glomeruli and interstitial area. The efficiency of renal artery group was higher than that of tail vein, anterior tibial muscle and renal parenchyma group (P<0.05). Immunohistochemical analysis revealed co-expression of ß-galactosidase with a roximal tubule marker, megalin, which suggested that ultrasound enhanced gene transfer into the proximal tubular epithelial cells. No ß-galactosidase expression was observed in the extrarenal organs. There were no evident pathological and biochemical changes after gene transfer. CONCLUSIONS: Ultrasound-mediated microbubble destruction can transfer gene into kidney via renal artery, tail vein, anterior tibial muscle and renal parenchyma. Compared with renal artery, administrating microbubbles via tail vein and anterior tibial muscle are more convenient and less vulnerarious.

[Transperitoneal transport of solute and IL-8 in dialysis-related peritonitis].

OBJECTIVE: To study the changes in solute transperitoneal transport and the IL-8 level at different time phases in dialysis-related peritonitis so as to understand the mechanism of solute transperitoneal transport. METHODS: Forty-two New Zealand white rabbits were randomly divided into three experimental groups (5 min, 24 h, and 48 h groups) and a control group. The rabbit model of peritoneal dialysis-related peritonitis was created. The plasma and effluent concentration of creatinine, glucose, total proteins, and albumin were determined respectively; the D/P values of creatinine, total proteins, and albumin, and the Dn/D0 values of glucose were calculated respectively. RESULTS: There was a significant difference in the D/P values of albumin at 120, 240, and 360 min between the 48 h group and the control group (P < 0.05); the D/P values of total proteins significantly increased at different time points in the 48 h group compared with the control group (P < 0.05); there was a significant difference in the creatinine D/P values and glucose Dn/D0 values between the 48 h group and the control group (P < 0.05). Compared with the control group, IL-8 and WBC obviously increased in the 48 h group (P < 0.05); the effluent IL-8 levels at different time points were positively correlated to the D/P values of the total proteins (P < 0.05). The effluent IL-8 levels at different time points after 60 min were positively correlated to the D/P values of albumin (P < 0.05). CONCLUSION: The mechanism of transperitoneal transport of the different molecule solutes varies. Both IL-8 and WBC can influence solute transperitoneal transport in peritoneal dialysis-related peritonitis.