Effects of intestinal resection on enterocyte apoptosis

Abstract

Intestinal resection results in increased numbers of villus and crypt enterocytes. This adaptive response occurs secondary to increased crypt cell proliferation early after resection. Apoptosis also increases in both crypt and villus compartments early after resection. Our aim was to evaluate change in proliferation and apoptosis later during the adaptive period. Eighteen rabbits undergoing 50% proximal intestinal resection were killed 7, 14, or 21 days after resection. Intestine at the resection margin was evaluated before and after resection for morphometry, crypt cell production rate (CCPR), and in situ end labeling of DNA fragmentation. Apoptotic cells were identified by morphologic evaluation. Villus height (382 ± 51 μm vs. 505 ± 131 μm) and crypt depth (121 ± 10 μm vs. 163 ± 21 μm; P <0.05) were significantly increased at 21 days. CCPR was also increased compared to preoperative values (5.8 ± 1.2 cells/hr vs. 8.6 ± 0.3, 7.9 ± 0.3, and 8.3 ± 1.6 cells/hr at 7, 14, and 21 days; P <0.05). Apoptotic index (apoptotic cells per 100 cells) was significantly increased in cells at the tip of the villus at 21 days (32 ± 7% vs. 19 ± 7%; P <0.05) but not in the lateral villus or total villus. Total cells per villus (83 ± 6 vs. 65 ± 3) and apoptotic cells per villus (9.2 ± 1.6 vs. 4.5 ± 2.5; P <0.05) were also greater at 21 days. Mean DNA fragmentation scores were similar before and after resection. The crypt apoptotic index was increased only in the lateral crypt at 14 days. Total cells per crypt increased after resection, and the number of apoptotic cells per crypt was increased at 7 and 14 days (2.5 ± 1.7 and 2.3 ± 1.1 vs. 0.6 ± 0.6 days; P <0.05). Thus the following conclusions were reached: (1) Apoptosis of villus tip cells remains elevated late in postresection adaptation; (2) crypt cell apoptosis returns to preoperative levels during the time interval when crypt cell proliferation is still stimulated; and (3) apoptosis in the crypt and villus compartments appears to be regulated independently.