| Objective:Diabetes,as a chronic metabolic disease,has attracted more and more attention for its cognitive impairment caused by lipid peroxides and reactive oxygen species.In this study,the effects of Panax quinquefolium L.-A cor us Tatarinowiion glycolipid metabolism,learning and memory ability,Nrf2/ARE signaling pathway related protein expression and brain morphological structure of diabetic mice were investigated,so as to clarify the reasons of Panax quinquefolium L.-Acorus Tatarinowiiimproving learning and memory ability of diabetic mice.Methods:a total of 140 SPF healthy male ICR mice were randomly divided into blank group（n=20）and model group（n=120）after adaptive feeding for 1 week.Blank group and model group were fed with normal diet and high-fat diet respectively for 4 weeks.Model group mice were intraperitoneally injected with low dose of streptozotocin（80mg·kg）-1)to replicate the diabetes model;Two weeks later,fasting blood glucose was measured in model mice,and fasting blood glucose was≥11.lmmol·L-1 Were included in the experiment.Diabetic mice were divided into Panax quinquefolium L.-Acorus Tatarinowii low-dose group（n=20）,Panax quinquefolium L.-Acorus Tatarinowii high-dose group（n=20）,diabetic group（n=25）and sitagliptin group（n=20）according to blood glucose.After 1 week of model replication,drug intervention was performed for 8 weeks in the Panax quinquefolium L.-AcorusTatarinowii low-dose group,Panax quinquefolium L.-Acorus Tatarinowii high-dose group,and group of sitagliptin.Fasting blood glucose and autonomic activity of each group of mice were dynamically measured at 2,4,6,and 8 weeks in the diabetes model replication.The model was replicated for 4 and 8 weeks for new object experiments.After 8 weeks of model replication,the Morris water maze and heat stimulation combined with the Y maze experiment were used to evaluate the learning and memory ability of each group of mice.Oral glucose tolerance,insulin tolerance,insulin,insulin resistance index,C-peptide,high density lipoprotein,low density lipoprotein,triglyceride and total cholesterol levels of mice in each group were determined.The changes of hippocampal neurons and morphological structure were observed by hematoxylin-eosin staining.The expressions of Nrf2,keapl and HO-1 proteins in the brain tissues of each group were detected by western blot.The levels of superoxide dismutase and malondialdehyde in brain tissues were determined.Results:Compared with the blank group,the serum protein and fasting blood glucose levels were significantly higher in the diabetic group（P<0.05,P<0.01）;Compared with diabetic group,fasting blood glucose in sitagliptin group was significantly decreased（P<0.01）.Compared with diabetic group,glycosylated serum protein levels in all drug groups were significantly decreased（P<0.01）.In oral glucose tolerance and insulin tolerance tests,the AUC of diabetic group was significantly higher than that of blank group（P<0.05,P<0.01）.Compared with the diabetic group,the oral glucose tolerance AUC was significantly decreased in the Panax quinquefolium L.-Acorus Tatarinowii high-dose group.Insulin tolerance AUC in all drug groups was significantly decreased（P<0.05,P<0.01）.Compared with blank group,c-peptide,insulin and insulin resistance index of diabetic group were significantly increased（P<0.01）;Compared with diabetic group,insulin,insulin resistance index and C-peptide in all drug groups were significantly decreased（P<0.01）.Compared with blank group,triglyceride and total cholesterol in diabetic group were significantly increased（P<0.01）,and high-density lipoprotein was significantly decreased（P<0.05）;Compared with diabetic group,the levels of high density lipoprotein in all drug groups were significantly increased（P<0.01,P<0.05）,and the levels of triglyceride and total cholesterol in sitagliptin and Panax quinquefolium L.-Acorus Tatarinowii high-dose groups were significantly decreased（P<0.01,P<0.05）.In the independent activity experiment,compared with the blank group,the number of independent activity in diabetic group was significantly decreased at 2 and 8 weeks（P<0.01）;Compared with diabetic group,the main active standing and active number of mice in each drug group were significantly increased at 4,6 and 8 weeks（P<0.01,P<0.05）.In the new object recognition experiment,compared with the blank group,the 8w relative recognition index of diabetic group was significantly decreased（P<0.01）,and the 8w relative recognition index of sitagliptin group and Panax quinquefolium L.-Acorus Tatarinowii high-dose groups was significantly increased（P<0.01,P<0.05）.In the Morris water maze experiment,the escape incubation period of the eighth time and test period in the diabetic group was significantly higher compared with the blank group,and that in the Panax quinquefolium L.-Acorus Tatarinowii high-dose groups and sitagliptin group compared with the diabetic group（P<0.05）.In the thermal stimulation and Y maze experiment,the number of learning and errors in diabetic mice increased significantly（P<0.01）;Compared with diabetic group,the learning times and error times of mice in all drug groups were significantly decreased（P<0.01）.Compared with blank group,Nrf2,HO-1 and keapl levels in diabetic group were significantly decreased（P<0.01）;Compared with diabetic group,the levels of Nrf2,HO-1 and keapl in the brain tissues of mice in all drug groups were significantly increased（P<0.01）.Compared with blank group,SOD level in diabetic group was significantly decreased（P<0.01）,MDA level was significantly increased（P<0.01）;Compared with diabetic group,SOD activity in brain tissue of mice in sitagliptin group and Panax quinquefolium L.-Acorus Tatarinowii high-dose group was significantly increased（P<0.05）,while MDA level was significantly decreased（P<0.01）.Conclusions:Diabetic mouse model was established by 4-week high-fat diet combined with low-dose streptozotocin.After 8 weeks of model replication,the spatial learning and memory ability of diabetic mice decreased.Panax quinquefolium L.-Acorus Tatarinowii may regulate oxidative stress homeostasis and reduce hippocampal neuron damage through Nrf2/ARE signaling pathway,thus improving spatial learning and memory ability of diabetic mice. |
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