重组降钙素原免疫小鼠对脓毒症诱导的急性肾损伤的保护作用

Protective effects of immunization with recombinant procalcitonin on sepsis - induced acutekidney injury in mouse

目的了解重组降钙素原（recombinant procalcitonin，rPCT）免疫小鼠对脓毒症诱导的急性肾损伤（AKI）的影响，并探索其可能的作用机制。方法10～12周龄健康雄性Balb／c小鼠30只随机分为假手术组（sham组，n=10），盲肠结扎穿孔组（CLP组，n=10），rPCT免疫组（免疫组，n=10）。使用盲肠结扎穿孔法（CLP）制作小鼠脓毒症动物模型。于CLP术前3周、2周、1周使用rPCT50斗g腹腔内注射免疫小鼠。CLP术后24h检测小鼠血清肌酐（SCr）、尿素氮（BUN）、降钙素原（PCT）、C-反应蛋白（CRP）、促炎介质和抗炎介质水平。处死小鼠，苏木精-伊红（HE）染色，观察小鼠肾组织病理学变化。结果与假手术组比较，CLP组小鼠SCr、BUN、TNF—d、IL-1及IL-6明显升高（P〈0．01）。与CLP组比较，免疫组小鼠SCr、BUN、TNF—d、IL-1及IL-6明显下降（P〈0．05）。假手术组小鼠。肾脏组织病理学基本正常；CLP组小鼠肾脏组织病理学显示，肾小管上皮细胞明显肿胀、脱落、空泡变性、刷状缘明显破坏。肾间质中性粒细胞浸润；免疫组小鼠肾小管上皮细胞肿胀、变性减轻。Kaplan—Meier生存分析显示，免疫组小鼠7d病死率较CLP组低（P〈0．05）。结论PCT在脓毒症相关性AKI的发病过程中可能促进炎症介质的释放，从而加重病情的进展。rPCT预先免疫小鼠，可以在-定程度上对脓毒症相关性AKI起保护作用。

Objective To investigate the renal protective effects of immunization with recombinant procalcitonin （rPCT） in mouse with sepsis - induced acute renal injury, and explore its possible mechanism. Methods Thirty male Balb/c mice were randomly divided into three groups, which were sham operation group （ sham group, n = 10）, cecal ligation and puncture （ CLP group, n = 10） group and immunization with rPCT group （immunization group, n = 10 ）. Sepsis model was reproduced in mice with cecal ligation and puncture （CLP）. Mice were immunized with 50 ixg of recombinant procalcitonin （PCT） 3 weeks, 2 weeks and 1 week respectively before CLP operation by intraperitoneal injection. Serum creatinine （SCr）, blood urea nitrogen （BUN）, PCT, tumor necrosis factor - ct （ TNF - ct）, interleukin - 1 [3 and 6 （ IL - 113, IL - 6 ） were determined 24 hours after CLP operation. Morphological changes of the kidney were observed by H＆E staining. Results Comparedwith sham group, serum urea nitrogen, TNF - c~, IL - 113 and IL - 6 were significantly high in CLP group （P 〈0.01）. However, when compared with CLP group, SCr, BUN, TNF- c~, IL- 113 and IL- 6 were significantly lower in immunization group. Kidney morphology in sham group was normal, while in CLP group, some pathological changes occurred, such as tubular epithelial cells swelling and exfoliation, vesicular degeneration, destruction of brush border and neutrophil infiltration of renal interstitium. These changes were ameliorated in immunization group. Kaplan - Meier survival analysis showed that 7 - days mortality of mouse in immunization group was lower than in CLP group. Conclusion PCT might promote the release of inflammatory mediators in the process of sepsis induced AKI, thus aggravate the disease progression. Immunization with rPCT might play a protective role on it.