Carter D, Einheber A, Bauer H, Rosen H, Burns W F
J Exp Med. 1966 Feb 1;123(2):251-66. doi: 10.1084/jem.123.2.251.
Uremic colitis of varying severity occurred in the majority of conventionalized rats dying after removal of both kidneys, but was not found in uremic conventionalized and germfree rats sacrificed preterminally, or in germfree and limited-flora rats dying from uremia, or in any of the controls. The lesions were restricted to the cecum and their incidence and severity paralleled a shorter duration of survival. Cardiovascular damage including focal myocardial necrosis and calcification and patchy aortic and coronary calcification were observed in uremic rats regardless of their microbial status. These lesions had a higher incidence, developed more rapidly, and were more severe in the germfree and limited-flora rats than in the conventionalized animals. The presence or severity of the lesions, however, did not correlate with survival time of rats dying from uremia or with total plasma calcium and inorganic phosphorus levels of individual animals. Generalized necrotizing arteritis was not observed. Wound healing was poor in all uremic rats regardless of microbial status. Focal infection was noted in a few conventionalized rats dying from uremia, did not correlate with survival time, and was absent in all other groups. Comparison of biochemical findings between uremic germfree and conventionalized rats show a higher blood urea nitrogen and elevated plasma indoxyl sulfate in the presence of a microbial flora and a greater amount of plasma inorganic phosphorus in its absence. Uremia resulted in a decrease in hematocrit and increase in plasma and muscle potassium that were similar for germfree and conventionalized rats. Plasma and muscle sodium, total plasma calcium, glucose, and total protein were essentially unchanged by microbial status or uremia. Because the foregoing differences in the metabolic and histopathologic changes of uremia are linked to the known difference in microbial status of the fasting bilaterally-nephrectomized rats that were studied, they are a tangible indication of ways by which the indigenous microbial flora and its composition may affect the course of acute uremia.
在大多数双侧肾脏切除后死亡的常规饲养大鼠中出现了不同严重程度的尿毒症性结肠炎，但在终末期前处死的尿毒症常规饲养大鼠和无菌大鼠中未发现，在死于尿毒症的无菌大鼠和有限菌群大鼠中也未发现，在任何对照组中同样未发现。病变局限于盲肠，其发生率和严重程度与较短的存活时间平行。无论微生物状态如何，在尿毒症大鼠中均观察到心血管损伤，包括局灶性心肌坏死和钙化以及散在的主动脉和冠状动脉钙化。这些病变在无菌大鼠和有限菌群大鼠中的发生率更高，发展更快，且比常规饲养动物更严重。然而，病变的存在或严重程度与死于尿毒症的大鼠的存活时间或个体动物的血浆总钙和无机磷水平无关。未观察到全身性坏死性动脉炎。无论微生物状态如何，所有尿毒症大鼠的伤口愈合都很差。在少数死于尿毒症的常规饲养大鼠中发现了局部感染，其与存活时间无关，在所有其他组中均未发现。尿毒症无菌大鼠和常规饲养大鼠的生化结果比较显示，在有微生物菌群存在时血尿素氮较高且血浆硫酸吲哚酚升高，在无微生物菌群时血浆无机磷含量更高。尿毒症导致血细胞比容降低，血浆和肌肉钾升高，无菌大鼠和常规饲养大鼠的情况相似。血浆和肌肉钠、血浆总钙、葡萄糖和总蛋白基本上不受微生物状态或尿毒症的影响。由于上述尿毒症代谢和组织病理学变化的差异与所研究的禁食双侧肾切除大鼠已知的微生物状态差异有关，它们切实表明了肠道固有微生物菌群及其组成可能影响急性尿毒症病程的方式。
