OBJECTIVETo analyze the relationship between cutaneous glycometabolic disorders and cutaneous neuropathy in diabetic rats, and to look for the mechanism of neuropathy and impaired wound healing.

METHODSEighty male SD rats were randomly divided into the normal control group (NC, n = 20), diabetic group (D, n = 20), aminoguanidine-interfered group (AI, n = 20), and insulin-interfered group (II, n = 20) by drawing lots. Diabetes was reproduced in rats of D, AI, and II groups with intraperitoneal injection of streptozotocin (STZ). Then, rats in AI group were fed with 100 mg×kg(-1)×d(-1) aminoguanidine, while rats in II group were subcutaneously injected with insulin for satisfactory control of blood glucose. Changes in mechanical and heat pain thresholds of pad of hind limb were measured at post injection week (PIW) 2, 4, 8. Skin specimens were collected during PIW 2-8 from pads for determination of contents of glucose, advanced glycation end product (AGE), substance P (SP), calcitonin gene-related peptide (CGRP), and observation of distribution and ultrastructure of skin nerve fibers. Data were processed with t test.

RESULTSThe mechanical and heat pain thresholds in D group at PIW 2 [(6.3 ± 1.5) g, (6.0 ± 0.9) s, respectively ] were obviously lower than those in NC group [(13.0 ± 3.2) g, (10.3 ± 1.2) s, with t value respectively 2.71, 3.42, P values all below 0.05]. Contents of glucose and AGE in skin tissue in D group were significantly increased when compared with those in NC group, especially at PIW 8 [(2.85 ± 0.33) mg/g, (31.7 ± 3.2) U/mg of hydroxyproline vs. (0.82 ± 0.22) mg/g, (22.2 ± 1.9) U/mg of hydroxyproline, with t value respectively 1.65, 6.47, P values all below 0.01]. The myelinated nerve fibers were edematous and degenerated, with axons compressed, while the unmyelinated nerve fibers were vacuolated, with microfilament and microtubule disorderly arranged. Content of SP in skin tissue in D group was lower as compared with that in NC group, especially at PIW 2 [(16.8 ± 3.4) pg/g vs. (28.5 ± 5.0) pg/g, t = 2.42, P < 0.01]. There was no obvious difference in content of CGRP between NC and D groups, and also in content of glucose in skin between D and AI groups. Compared with those in D group, content of AGE in AI group at PIW 8 was decreased markedly [(27.2 ± 1.4) U/mg of hydroxyproline, t = 3.38, P < 0.05]; contents of glucose and AGE in II group at PIW 8 were significantly decreased [(1.42 ± 0.38) mg/g, (23.6 ± 1.3) U/mg of hydroxyproline, with t value respectively 1.74, 8.17, P < 0.05 or P < 0.01]. Compared with that in D group, contents of SP in AI and II groups were increased, with a delay in time of trough value. Content of CGRP showed no obvious difference among D, AI, and II groups.

CONCLUSIONSHigh glucose and accumulation of AGE are key mediators of cutaneous neuropathy and impaired wound healing in diabetes mellitus, which confirms that diabetic wound takes an atypical footing during wound repairing. Aminoguanidine and insulin can reduce contents of glucose and AGE in diabetic skin tissue, and ameliorate diabetic cutaneous neuropathy.