HEPATIC-INJURY ASSOCIATED WITH SMALL-BOWEL BACTERIAL OVERGROWTH IN RATS IS PREVENTED BY METRONIDAZOLE AND TETRACYCLINE
HEPATIC-INJURY ASSOCIATED WITH SMALL-BOWEL BACTERIAL OVERGROWTH IN RATS IS PREVENTED BY METRONIDAZOLE AND TETRACYCLINE
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DOI：
10.1016/0016-5085(91)90224-9
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发表时间：
1991-02-01
期刊：
影响因子：
29.4
通讯作者：
SARTOR, RB
中科院分区：
文献类型：
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作者：
LICHTMAN, SN;KEKU, J;SARTOR, RB
易受影响的大鼠菌株发生肝胆损伤后，手术创造的自我填补盲环，导致小肠细菌过度生长。腔内细菌或其细胞壁聚合物与病变的发病机制有关，因为假手术大鼠和具有自我排空盲环的大鼠，细菌数量只有轻微增加，没有发生肝损伤。在本研究中，从术后1天或22天开始连续给予不同活性谱的抗生素，以确定哪些肠道菌群可能对小肠细菌过度生长的大鼠肝损伤的发展负责。术后4周，未使用抗生素的自充盈盲环Lewis大鼠肝脏组织学评分（8.2±1.3比0.7±0.4）和血浆天冬氨酸转氨酶水平（269±171比84±24）均高于假手术大鼠，P< 0.001。口服庆大霉素以及口服和腹腔内结合内毒素的多粘菌素B不能预防自充性盲环大鼠的肝损伤。然而，术后第1天开始持续口服甲硝唑和四环素治疗可减轻肝损伤（组织学评分3.0±1.8,2.9±1.1；天冬氨酸转氨酶87±25,98±34；与不使用抗生素的自充血盲环相比，p < 0.001）。与未接受抗生素治疗的自充性盲环大鼠相比，甲硝唑对实验性小肠细菌过度生长后需要12周发生肝损伤的Wistar大鼠也有保护作用（组织学评分10.4±1.3比0.7±1.1，天冬氨酸转氨酶273±239比76±20，P< 0.001）。当大鼠在自填盲环手术22天后开始甲硝唑治疗时，天冬氨酸转氨酶升高值在接下来的77天内降至正常，最终组织学评分正常。所有自充性盲环大鼠的腹膜、肝脏、脾脏和血液培养均为阴性，但无论抗生素治疗如何，约75%的肠系膜淋巴结培养均为阳性。由于拟杆菌类与自填盲环大鼠的维生素b12和双糖酶缺乏有关，我们使用选择性培养技术记录了这些生物在盲环中的存在或不存在。甲硝唑和四环素消除拟杆菌。但多粘菌素B和庆大霉素没有。这些结果表明拟杆菌。其他厌氧菌可能在小肠细菌过度生长引起肝损伤的发病机制中起重要作用。
Susceptible rat strains develop hepatobiliary injury following the surgical creation of self-filling blind loops that cause small bowel bacterial overgrowth. Luminal bacteria or their cell wall polymers were implicated in the pathogenesis of the lesions because sham-operated rats and rats with self-emptying blind loops, having only slightly increased bacterial counts, did not develop hepatic injury. In this study, antibiotics with different spectra of activities were continuously administered starting 1 day or 22 days after surgery to determine which intestinal flora may be responsible for the development of hepatic injury in rats with small bowel bacterial overgrowth. Four weeks following surgery, Lewis rats with self-filling blind loops receiving no antibiotics had elevated liver histology scores (8.2 ± 1.3 vs. 0.7 ± 0.4) and plasma aspartate aminotransferase levels (269 ±171 vs. 84 ± 24) compared with sham-operated rats,P< 0.001. Oral gentamicin as well as oral and intraperitoneal polymyxin B, which binds endotoxin, did not prevent hepatic injury in rats with self-filling blind loops. However, oral metronidazole and tetracycline therapy continuously administered beginning 1 day after surgery diminished hepatic injury (histology score 3.0 ± 1.8, 2.9 ± 1.1; aspartate aminotransferase 87 ± 25, 98 ± 34; respectivelyP< 0.001 compared with self-filling blind loops receiving no antibiotics). Metronidazole also protected Wistar rats that require 12 weeks to develop hepatic injury following experimentally induced small bowel bacterial overgrowth compared with rats with self-filling blind loops that received no antibiotic treatment (histology score 10.4 ± 1.3 vs. 0.7 ± 1.1 and aspartate aminotransferase 273 ± 239 vs. 76 ± 20,P< 0.001). When rats started metronidazole therapy 22 days after self-filling blind loop surgery, elevated aspartate aminotransferase values decreased to normal during the next 77 days and final histology scores were normal. All rats with self-filling blind loops had negative peritoneal, liver, spleen, and blood cultures but approximately 75% of mesenteric lymph node cultures were positive irrespective of antibiotic treatment. BecauseBacteroidesspecies have been implicated in causing vitamin B12and disaccharidase deficiencies in rats with self-filling blind loops, we documented the presence or absence of these organisms from blind loops using selective culture techniques. Metronidazole and tetracycline eliminatedBacteroidessp. from blind loops, but polymyxin B and gentamicin did not. These results suggest thatBacteroidessp. and possibly other anaerobic bacteria play an important role in the pathogenesis of hepatic injury associated with small bowel bacterial overgrowth.