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

Abstract

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.