Wang T, Cheng H H, Heimbürger O, Chen C, Waniewski J, Bergström J, Lindholm B
Department of Clinical Science, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Kidney Int. 1999 Feb;55(2):667-73. doi: 10.1046/j.1523-1755.1999.00279.x.
We have recently shown that the addition of hyaluronan to peritoneal dialysis solution could decrease the peritoneal fluid absorption rate, possibly through decreasing peritoneal tissue hydraulic conductivity. The physical-chemical properties of hyaluronan were found to be both molecular weight and concentration dependent. In this study, we investigated the effects of different molecular weight as well as different concentrations of hyaluronan on the peritoneal fluid kinetics.
A four-hour dwell study was performed in 48 male Sprague-Dawley rats (6 rats in each group) with 131I albumin (RISA) as an intraperitoneal volume marker. Each rat was intraperitoneally injected with 25 ml of 1.36% glucose dialysate alone (control) or with 0.01% hyaluronan (HA) with different molecular weights [85,000 (HA85K group), 280,000 (HA280K group), 500,000 (HA500K group), and 4,000,000 (HA4M group) molecular wt] or with a different concentrations of hyaluronan [(molecular wt 500,000); 0.01% (0.01% HA group), 0.05% (0.05% HA group), 0.1% (0.1% HA group), and 0.5% (0.5% HA group) hyaluronan].
The peritoneal fluid absorption rate (as assessed by the RISA elimination rate, KE) was significantly decreased in the HA500K and H4M groups as well as in all the different concentration groups (with molecular wt 500,000) as compared with the control group, resulting in significantly higher net fluid removal in these groups (except for the H4M group) as compared with the control group. In the 0.5% HA group (but not in the other hyaluronan groups), the direct lymphatic absorption (KEB) was also significantly decreased. The transcapillary ultrafiltration rate (Qu) was significantly lower in the HA4M group as compared with the control group but significantly higher in the 0.05% HA (and tended to be higher in the 0.1% HA group) as compared with the other groups. No difference in Qu was found between the 0.5% HA group as compared with the control group, despite a more marked decrease in KE in this group as compared with the H4M group. There were no significant differences in KE, Qu, and net fluid removal between the HA85K and HA280K groups and the control group.
Our results suggest that (a) the addition of hyaluronan to dialysate could decrease peritoneal fluid absorption and thus increase the net ultrafiltration; this effect appears to be both size dependent and concentration dependent. (b) High molecular weight fraction of hyaluronan may also decrease the transcapillary Qu by decreasing tissue hydraulic conductivity. (c) A higher concentration of hyaluronan in dialysate resulted in a more marked decrease in peritoneal fluid absorption (absorption to peritoneal tissues as well as direct lymphatic absorption), possibly through both decreasing tissue hydraulic conductivity and increasing fluid viscosity. (d) Decreasing tissue hydraulic conductivity by adding a high concentration of hyaluronan to dialysate does not decrease the transcapillary ultrafiltration, possibly because the osmotic effect of hyaluronan may counterbalance the decrease in transcapillary ultrafiltration because of the decrease in tissue hydraulic conductivity.
我们最近发现，向腹膜透析液中添加透明质酸可能会降低腹膜液吸收速率，这可能是通过降低腹膜组织水导率实现的。研究发现透明质酸的物理化学性质既取决于分子量，也取决于浓度。在本研究中，我们调查了不同分子量以及不同浓度的透明质酸对腹膜液动力学的影响。
对48只雄性Sprague-Dawley大鼠（每组6只）进行了为期4小时的驻留研究，以131I白蛋白（RISA）作为腹腔内体积标志物。每只大鼠腹腔内单独注射25ml 1.36%葡萄糖透析液（对照组），或注射含不同分子量[85,000（HA85K组）、280,000（HA280K组）、500,000（HA500K组）和4,000,000（HA4M组）分子量]的0.01%透明质酸（HA），或注射含不同浓度透明质酸[（分子量500,000）；0.01%（0.01%HA组）、0.05%（0.05%HA组）、0.1%（0.1%HA组）和0.5%（0.5%HA组）透明质酸]。
与对照组相比，HA500K组和H4M组以及所有不同浓度组（分子量500,000）的腹膜液吸收速率（通过RISA清除率KE评估）显著降低，导致这些组（H4M组除外）的净液体清除量显著高于对照组。在0.5%HA组（但在其他透明质酸组中未出现），直接淋巴吸收（KEB）也显著降低。与对照组相比，HA4M组的跨毛细血管超滤率（Qu）显著更低，但与其他组相比，0.05%HA组（0.1%HA组也有升高趋势）的Qu显著更高。与对照组相比，0.5%HA组的Qu没有差异，尽管该组的KE比H4M组下降得更明显。HA85K组和HA280K组与对照组之间的KE、Qu和净液体清除量没有显著差异。
我们的结果表明：（a）向透析液中添加透明质酸可降低腹膜液吸收，从而增加净超滤；这种效应似乎既取决于大小，也取决于浓度。（b）透明质酸的高分子量部分也可能通过降低组织水导率来降低跨毛细血管Qu。（c）透析液中较高浓度的透明质酸导致腹膜液吸收（对腹膜组织的吸收以及直接淋巴吸收）更显著降低，这可能是通过降低组织水导率和增加液体粘度实现的。（d）通过向透析液中添加高浓度透明质酸来降低组织水导率并不会降低跨毛细血管超滤，这可能是因为透明质酸的渗透作用可能会抵消由于组织水导率降低而导致的跨毛细血管超滤的降低。
