Flessner Michael F, Credit Kimberly, Henderson Karla, Vanpelt Heather M, Potter Rebecca, He Zhi, Henegar Jeffrey, Robert Barry
Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505, USA.
J Am Soc Nephrol. 2007 Aug;18(8):2294-302. doi: 10.1681/ASN.2006121417. Epub 2007 Jun 28.
Most current animal models that are used to study effects of long-term peritoneal exposure to dialysis solutions use an indwelling catheter for daily injections. It was hypothesized that the presence of a foreign body in the peritoneal cavity (PC) might alter the inflammatory response to the solutions and that the response would depend on exposure duration. For addressing these, long-term injections were carried out for 2 to 8 wk in 90 Sprague-Dawley rats: 40 via a subcutaneous port connected to a silicone catheter tunneled to the PC, 40 via direct needle injection, and 10 noninjected, age-control rats. Daily volumes were 30 to 40 ml of filter-sterilized, bicarbonate-buffered solutions that contained 4% dextrose. After 2, 4, 6, and 8 wk, anesthetized rats underwent transport experiments with a chamber affixed to the abdominal wall to determine mass transfer coefficients of mannitol (MTC(mannitol)) and albumin (MTC(BSA)), osmotic filtration flux (J(osm)), and hydrostatic pressure-driven flux. After the rats were killed, tissues were collected for measurement of peritoneal thickness, vascular density, and immunohistochemical staining. ANOVA demonstrated significant (P < 0.01) differences in thickness, vessel density, MTC(mannitol), and MTC(BSA) among the groups at the various time intervals and in overall means. Differences among the groups were less pronounced for hydrostatic pressure-driven flux and J(osm). Vessel density, MTC(mannitol), MTC(BSA), and J(osm) were dependent on injection duration (P < 0.01). There were marked differences between the needle injection and catheter injection groups at various intervals in the expression of three cytokines. It is concluded that the histologic and functional response depends on the duration of injection with animals that are exposed for as little as 2 wk demonstrating alterations. These findings confirm the hypothesis that the presence of a PC catheter increases inflammatory response to sterile solutions as evidenced by the structural and functional changes in the peritoneal barrier.
目前大多数用于研究长期腹膜暴露于透析液影响的动物模型，都使用留置导管进行每日注射。据推测，腹腔（PC）中异物的存在可能会改变对透析液的炎症反应，且这种反应将取决于暴露持续时间。为了验证这些推测，对90只Sprague-Dawley大鼠进行了2至8周的长期注射：40只通过连接到经皮下隧道插入PC的硅胶导管的皮下端口进行注射，40只通过直接针头注射，10只未注射作为年龄对照大鼠。每日注射量为30至40毫升经滤器灭菌、碳酸氢盐缓冲且含有4%葡萄糖的溶液。在2、4、6和8周后，对麻醉的大鼠进行运输实验，将一个腔室固定在腹壁上，以测定甘露醇的质量传递系数（MTC(甘露醇)）和白蛋白的质量传递系数（MTC(牛血清白蛋白)）、渗透过滤通量（J(渗透)）和静水压驱动通量。大鼠处死后，收集组织以测量腹膜厚度、血管密度和免疫组织化学染色。方差分析表明，在各个时间间隔和总体均值方面，各组之间在厚度、血管密度、MTC(甘露醇)和MTC(牛血清白蛋白)上存在显著（P < 0.01）差异。静水压驱动通量和J(渗透)的组间差异不太明显。血管密度、MTC(甘露醇)、MTC(牛血清白蛋白)和J(渗透)取决于注射持续时间（P < 0.01）。在不同时间间隔，针头注射组和导管注射组在三种细胞因子的表达上存在明显差异。得出的结论是，组织学和功能反应取决于注射持续时间，暴露仅2周的动物就表现出变化。这些发现证实了如下推测：PC导管的存在会增加对无菌溶液的炎症反应，腹膜屏障的结构和功能变化证明了这一点。
