Singhal P C, Pan C Q, Sagar S, Gibbons N, Valderrama E
Department of Medicine, Long Island Jewish Medical Center, New Hyde Park, N.Y. 11042, USA.
Nephron. 1995;70(2):229-34. doi: 10.1159/000188589.
Since increased mesangial accumulation of matrix has been considered to be an important event in the development of focal glomerulosclerosis, we investigated whether morphine, an active metabolite of heroin, can modulate mesangial accumulation of immune complexes. Control or morphine-dependent rats were administered intraperitoneal ferritin (8 mg/100 g body weight) daily for 6 weeks. Body weight, blood pressure, serum creatinine, 24-hour urinary protein and creatinine excretion rates were measured at 3-week intervals. Rats were sacrificed at the end of 6 weeks and kidney tissue was studied by light, immunofluorescence and electron microscopy. Serum creatinine levels and urinary protein excretion rates were not different between control and morphine-dependent rats. All morphine-dependent rats developed hematuria, whereas only 1 control rat developed hematuria. Light microscopy revealed no proliferation of mesangial cells and only a minimal increase in the mesangial matrix. Electron-microscopic studies showed deposition of immune complexes in the mesangial region. Mesangial cells showed aggregation of ferritin in lysosomes. Immunofluorescence studies revealed the presence of IgG staining predominantly in the mesangial region. The majority (60%) of morphine-dependent rats showed a diffuse mesangial deposition of IgG when compared to control rats (83%) who showed only focal deposition. These results indicate that morphine enhances deposition of immune complexes in the mesangium. Morphine-induced matrix but may also change its quality. This may play a pathogenic role in the development of glomerular lesions in patients who abuse opiates.
由于系膜基质积聚增加被认为是局灶性肾小球硬化发展过程中的一个重要事件,我们研究了海洛因的活性代谢产物吗啡是否能调节免疫复合物在系膜的积聚。对对照大鼠或吗啡依赖大鼠每天腹腔注射铁蛋白(8毫克/100克体重),持续6周。每隔3周测量体重、血压、血清肌酐、24小时尿蛋白和肌酐排泄率。在6周结束时处死大鼠,通过光镜、免疫荧光和电子显微镜研究肾脏组织。对照大鼠和吗啡依赖大鼠的血清肌酐水平和尿蛋白排泄率没有差异。所有吗啡依赖大鼠均出现血尿,而只有1只对照大鼠出现血尿。光镜检查显示系膜细胞无增殖,系膜基质仅略有增加。电子显微镜研究显示免疫复合物沉积于系膜区。系膜细胞的溶酶体中可见铁蛋白聚集。免疫荧光研究显示IgG染色主要存在于系膜区。与仅表现为局灶性沉积的对照大鼠(83%)相比,大多数(60%)吗啡依赖大鼠表现为IgG在系膜区的弥漫性沉积。这些结果表明,吗啡可增强免疫复合物在系膜的沉积。吗啡不仅可诱导基质形成,还可能改变其性质。这可能在滥用阿片类药物患者的肾小球病变发展中起致病作用。