| Objective:Diabetes is a metabolic disease with the characteristics of elevating blood sugar, which is caused by lacking insulin secretion or insulin resistance. The complication of cognitive impairment caused by diabetes increases with years, and it seriously affects patients'daily life. Hydrogen sulfide (H2S) is a new type of endogenous gaseous signal molecule, which plays an important role in some nerve protective functions such as anti-apoptosis, anti-oxidative stress, anti endoplasmic reticulum stress, and enhancing the plasticity of nerve cells in hippocampus and so on. Our previous study found that H2S has the function of alleviating cognitive impairment and hippocampal injury in diabetic rats, but the mechanism remains unclear. Polyamines exisits in living organismsare widely, and it is a low molecular aliphatic nitrogen compound that not only is indispensable to maintenance of normal physiological functions, but also plays an important role in some nerve protection function such as regulating neurotransmitter receptors and the growth of nerve, enhancing the plasticity of synapsis, and improving the ability of learning and memory and so on. As a result, the present work is aim to test whether polyamines signaling pathway in hippocampus is involved in the protective effects of H2S on diabetes-induced cognitive impairment and hippocampal injury.Method:Adult male Sprague Dawley (SD) rats were given intraperitoneal injection with sterptozotocin (STZ,55 mg/kg) one time.3 days later, if the tail vein blood glucose more than 16.7mmol/L, it is regarded as a successful model; the cognitive function was evaluated by novel object recognition test, Y-maze test, shuttle box test, and Morris water maze; the morphologic changes of hippocampal were observed by HE staining; apoptosis of hippocampal neuron was measured by Tunel assay; the expression of Bcl-2 and Bax in hippocampus was detected by Western blot.Result:1. H2S improves the cognitive function in diabetic rats. After diabetic rats were treated with NaHS (the donor of H2S,30,100 ?mol/kg/d, ip) for 30 days, (1) novel object recognition test showed that NaHS (100 ?mol/kg) significantly improved the new object recognition index in diabetic rats; Y-maze test showed that NaHS (100?mol/kg) significantly increased the alternate correct rate in diabetic rats; shuttle box test showed that NaHS (100 ?mol/kg) significantly increased the avoidance rate and reduced the latency of mean active avoidance response in diabetic rats; Morris water maze test showed that NaHS (100 ?mol/kg) significantly reduced the latency in search of platform, increased the times of acrossing original platform, and increased the time in target quadrant (the quadrant of discharging original platform) in diabetic rats. These results indicated that H2S improves the cognitive function in diabetic rats.2. H2S reduces hippocampal injury in diabetic rats. After the diabetic rats were treated with NaHS (30,100 ?mol/kg/d, ip) for 30 days, (1) HE staining showed that NaHS (100 ?mol/kg) significantly made hippocampal cells more regularly, reduced dissolved nucleus and the loss of hippocampal neurons in CA3 of diabetic rats; (2) Tunel assay showed that NaHS (100?mol/kg) significantly reduced apoptosis of hippocamal cells in CA3 of diabetic rats; (3) Western blot showed that NaHS (100?mol/kg) significantly reduced the expression of Bcl-2 and increased the expression of Bax in hippocampus of diabetic rats. These results indicated that H2S prevents hippocampal injury in diabetic rats.3. Difluoromethylornithine (DFMO) reverses the ability of H2S to improve the cognitive function in diabetic rats. After the diabetic rats were co-treated with NaHS (100 ?mol/kg/d, ip) and DFMO (5?g/d, icv) for 30 days, (1) novel object recognition test showed that DFMO attenuated NaHS (100 ?mol/kg)-induced increase in the index of new object recognition of diabetic rats; (2) Y-maze test showed that DFMO attenuated NaHS (100 ?mol/kg)-increased the alternate correct rate in diabetic rats; (3) shuttle box test showed that DFMO reversed NaHS (100?mol/kg)-induced increase in avoidance rate and decrease in the latency of mean active avoidance response in diabetic rats; (4) the Morris water maze test showed that DFMO attenuated NaHS (100 ?mol/kg)-induced decrease in the latency in search of platform, increased in the times of acrossing original platform, and increased in the time in target quadrant (the quadrant of discharging original platform) of diabetic rats. These results indicated that H2S improves the cognitive function in diabetic rats depond on polyaminess signaling pathway.4. DFMO reverses the ability of H2S to improve hippocampal injury of in diabetic rats. After the diabetic rats were co-treated with NaHS (100?mol/kg/d, ip) and DFMO (5?g/d, icv) for 30 day, (1) HE staining showed that DFMO reversed the affect of NaHS (100 ?mol/kg) improving the arrangement of hippocampal neuron, reducing nucleus dissolved and the loss hippocampal neurons in CA3 of diabetic rats; (2) Tunel assay showed that DFMO attenuated NaHS (100?mol/kg)-reduced apoptosis of hippocamal cells in CA3 of diabetic rats; (3) Western blot showed that DFMO attenuated NaHS (100 ?mol/kg)-induced increase in expressing Bcl-2 and decrease in expressing Bax of hippocampus in diabetic rats. These results indicated that H2S inhibits the hippocampal injury in diabetic rats depond on polyamines signaling pathway.Conclusion:Polyaminess signaling pathway is required for H2S-improved cognitive impairment and hippocampal injury in diabetic rats. |
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