Treatment with Cyclohexenonic Long-Chain Fatty Alcohol Reverses Diabetes-Induced Tracheal Dysfunction in the Rat

In this study, we tried to elucidate the effect of cyclohexenonic long-chain fatty alcohol (N-hexacosanol) on tracheal dysfunction in diabetic rats. Diabetes was induced in 8-week-old male Sprague-Dawley rats by administering an intraperitoneal injection of 50 mg/kg streptozotocin. Non-diabetic control rats received an injection of citrate-phosphate buffer alone. Four weeks after the induction of diabetes, rats were randomly divided into 5 groups: age-matched non-diabetic control rats (group A); 4-week diabetic rats without N-hexacosanol treatment (group B); diabetic rats treated with vehicle (group C), and diabetic rats treated with N-hexacosanol at a dose of 2 or 8 mg/kg i.p. every day for the following 4 weeks (group D and group E, respectively; n = 6–8 animals in each group). Serum glucose and insulin levels were determined, as were the contractile responses induced by carbachol and 100 mmol/l KCl. The participation of M2 and M3 receptors was investigated in the trachea by real-time polymerase chain reaction (PCR), hematoxylin and eosin (HE) and immunohistochemical staining. Hypertrophy of airway smooth muscle was observed in diabetic rats, and was ameliorated by treatment with N-hexacosanol. Treatment with either 2 or 8 mg/kg N-hexacosanol did not alter diabetic rat status, i.e., body weight, serum glucose or serum insulin levels, but it significantly reversed the decrease in tracheal wall thickness and diabetes-induced hypercontractility in the rat trachea. In the immunohistochemical studies, muscarinic M2 and M3 receptors were expressed in the airway smooth muscle, the elastic fibers, the fibroblast and the surface of epithelium, and these expressions were not altered by either induction of diabetes or N-hexacosanol treatment. The expression of M3 muscarinic receptor mRNAs in the trachea tended to be increased by the induction of diabetes and normalized when treated with N-hexacosanol. Our data indicate that N-hexacosanol could reverse diabetes-induced hypercontractility in the rat trachea.