Amore A, Coppo R, Roccatello D, Piccoli G, Mazzucco G, Gomez-Chiarri M, Lamm M E, Emancipator S N
Institute of Pathology, Case Western Reserve University, Cleveland, Ohio.
Lab Invest. 1994 Jan;70(1):68-77.
In humans, alcoholic liver disease is frequently associated with IgA mesangial deposits, microscopic hematuria and a small amount of proteinuria, identifying a secondary form of IgA nephropathy. Alcoholic liver disease is almost always associated with nutritional deficiencies.
In order to examine the relationship between alcohol intake and/or inadequate diet and IgA nephropathy, groups of 4 week-old-male Lewis rats were maintained on a lipotrope-deficient (LD) diet (N = 20), intragastric infusions of a commercial whiskey (1.5 ml/100 gm body weight) three times a week, and regular chow (N = 23) or both intragastric whiskey infusion and an LD diet (N = 17). A fourth control group (N = 19) was given no whiskey and normal chow.
All rats given the LD diet had marked steatosis and elevated "liver" enzymes. Changes were more severe, and with early bridging fibrosis and nodule formation in those also given whiskey, associated with increased hepatic content of mRNA encoding transforming growth factor-beta. A moderate steatosis without alteration in serum enzymes or transforming growth factor-beta expression was found in rats given whiskey (all p < 0.0001) compared with controls. IgA accumulated in hepatic sinusoids instead of in canaliculi and bile ducts, suggesting impaired transport of IgA and IgA immune complexes from blood to bile, in rats given an LD diet and/or whiskey infusion. A moderate increase in mesangial matrix was observed only in rats given both whiskey and an LD diet. Bright granular IgA and mild granular C3 mesangial deposits and electron-dense deposits were evident in 63 to 70% of experimental rats (all p < 0.001) versus only trace deposits in 5 to 11% of controls. Moderate IgG codeposits were present in 34 to 55% of rats given the LD diet and/or whiskey (all p < 0.02), versus trace deposits in 10% of controls. Significant hematuria and proteinuria were observed in rats given the LD diet and/or whiskey (p < 0.0001) versus controls. Intestinal permeability measured by xylose absorption was significantly increased relative to controls only in rats given both whiskey and the LD diet (p < 0.001). Serum IgA specific for selected alimentary antigens was increased relative to controls in 75 to 100% of the experimental rats.
The combination of LD diet and alcohol intake, which mimics the human alcoholic condition, promotes hepatic and renal changes, leading to hepatocellular injury and a secondary form of IgA nephropathy.
在人类中，酒精性肝病常与IgA系膜沉积、镜下血尿和少量蛋白尿相关，提示为IgA肾病的一种继发形式。酒精性肝病几乎总是与营养缺乏有关。
为了研究酒精摄入和/或饮食不足与IgA肾病之间的关系，将4周龄雄性Lewis大鼠分为几组，分别给予低脂饮食（LD）（N = 20）、每周三次胃内输注市售威士忌（1.5 ml/100 g体重）、常规饲料（N = 23），或同时给予胃内威士忌输注和LD饮食（N = 17）。第四个对照组（N = 19）不给予威士忌，给予正常饲料。
所有给予LD饮食的大鼠均有明显的脂肪变性和“肝脏”酶升高。在同时给予威士忌的大鼠中，变化更严重，出现早期桥接纤维化和结节形成，与编码转化生长因子-β的mRNA肝脏含量增加有关。与对照组相比，给予威士忌的大鼠有中度脂肪变性，但血清酶或转化生长因子-β表达无改变（所有p < 0.0001）。在给予LD饮食和/或威士忌输注的大鼠中，IgA积聚在肝血窦而非胆小管和胆管中，提示IgA和IgA免疫复合物从血液到胆汁的转运受损。仅在同时给予威士忌和LD饮食的大鼠中观察到系膜基质中度增加。63%至70%的实验大鼠出现明亮的颗粒状IgA和轻度颗粒状C3系膜沉积以及电子致密沉积（所有p < 0.001），而对照组仅5%至11%有微量沉积。在给予LD饮食和/或威士忌的大鼠中，34%至55%有中度IgG共沉积（所有p < 0.02），而对照组为10%有微量沉积。与对照组相比，给予LD饮食和/或威士忌的大鼠出现明显血尿和蛋白尿（p < 0.0001）。仅在同时给予威士忌和LD饮食的大鼠中，通过木糖吸收测量的肠道通透性相对于对照组显著增加（p < 0.001）。75%至100%的实验大鼠血清中针对选定食物抗原的IgA相对于对照组增加。
模仿人类酒精性状况的LD饮食和酒精摄入相结合，会促进肝脏和肾脏变化，导致肝细胞损伤和IgA肾病的继发形式。
