Pan C Q, Singhal P C
Department of Medicine, Long Island Jewish Medical Center, New Hyde Park, New York 11042.
Proc Soc Exp Biol Med. 1994 Jan;205(1):29-34. doi: 10.3181/00379727-205-43673.
Focal glomerulosclerosis is the predominant glomerular lesion in patients with drug addiction. Since mesangial expansion has been considered a precursor of glomerulosclerosis we investigated whether the use of these drugs can cause accumulation of macromolecules into mesangium which may contribute to the expansion of mesangium. The majority of drug addicts at times take drugs in groups and may thus be exposed to a variety of drugs (cocaine, alcohol, and heroin). Therefore, we studied the effect of cocaine, alcohol, and morphine alone or in combination on the accumulation of radiolabeled human immunoglobulin-G (IgG) aggregates (AHIgG125I) into glomeruli/mesangium. Cocaine enhanced accumulation of AHIgG125I at 8 hr. Glomerular levels of AHIgG125I levels were also higher in morphine treated rats when compared with untreated animals. Alcohol did not alter the deposition of AHIgG125I. But at an earlier time (4 hr) alcohol enhanced the effect of cocaine on accumulation of IgG aggregates into the mesangium. The combined effects of morphine and cocaine, or morphine and alcohol were not different than the effect of morphine alone. The enhanced accumulation of phlogogenic macromolecules into the mesangium may not only increase the quantity of mesangial matrix but may also alter the quality of matrix. This may be playing an important role in the development of glomerular injury.
局灶性节段性肾小球硬化是药物成瘾患者主要的肾小球病变。由于系膜扩张被认为是肾小球硬化的先兆,我们研究了这些药物的使用是否会导致大分子物质在系膜中蓄积,而这可能会促使系膜扩张。大多数吸毒者有时会群体吸毒,因此可能接触多种药物(可卡因、酒精和海洛因)。所以,我们研究了可卡因、酒精和吗啡单独或联合使用对放射性标记的人免疫球蛋白G(IgG)聚集体(AHIgG125I)在肾小球/系膜中蓄积的影响。可卡因在8小时时增强了AHIgG125I的蓄积。与未治疗的动物相比,吗啡治疗的大鼠肾小球中AHIgG125I水平也更高。酒精未改变AHIgG125I的沉积。但在较早时间(4小时),酒精增强了可卡因对IgG聚集体在系膜中蓄积的作用。吗啡与可卡因或吗啡与酒精的联合作用与单独使用吗啡的作用无差异。促炎大分子物质在系膜中蓄积增加不仅可能会增加系膜基质的量,还可能改变基质的性质。这可能在肾小球损伤的发展中起重要作用。