PATHOGENESIS OF MUCOSAL INJURY IN BLIND LOOP SYNDROME - BRUSH-BORDER ENZYME-ACTIVITY AND GLYCOPROTEIN DEGRADATION

The effect of intestinal bacterial overgrowth on brush border hydrolases and brush border glycoproteins was studied in nonoperated control rats, control rats with surgically introduced jejunal self-emptying blind loops and rats with surgically introduced jejunal self-filling blind loops. Data were analyzed from blind loop segments, segments above and below the blind loops and 3 corresponding segments in the nonoperated controls. Rats with self-filling blind loops had significantly greater fat excretion than controls and exhibited significantly lower conjugated:free bile salt ratios in all 3 segments. Maltase, sucrase and lactase activities were significantly reduced in homogenates and isolated brush borders from the self-filling blind loop but alkaline phosphatase was not affected. The relative degradation rate of homogenate and brush border glycoproteins was assessed by a double-isotope technique involving the injection of D-6-3H glucosamine 3 h and D-U-14C glucosamine 19 h before sacrifice and recorded as a 3H:14C ratio. The relative degradation rate in both homogenate and brush border fractions was significantly greater in most segments from rats with self-filling blind loops. In the upper and blind loop segments from rats with self-filling blind loops, the 3H:14C ratios were higher in the brush border membrane than in the corresponding homogenates, indicating that the increased rates of degradation primarily involve membrane glycoproteins. Incorporation of D-6-3H glucosamine by brush border glycoproteins was not reduced in rats with self-filling blind loops, suggesting that glycoprotein synthesis was not affected. Polyacrylamide gel electrophoresis of brush border glycoproteins from the contaminated segments indicated that the large MW glycoproteins, which include many of the surface hydrolases, were degraded most rapidly. Brush border maltase, isolated by immunoprecipitation, had 3H:14C ratios characteristic of the most rapidly degraded glycoproteins. Bacteria enhance the destruction of intestinal surface glycoproteins including disaccharidases. Since alkaline phosphatase, a glycoprotein, is not affected, the destruction is selective and presumably involves only the most exposed membrane components.