RESUMO
Objective To explore the regulatory effeet of Qifu Yin ( QFY) on JAK2/STAT3 pathway in rats with type 2 diabetic cognitive impairment.Methods A small dose of STZ combined with high-fat and high- sugar feed was used to build the model.After success, they were divided into model group, QFY low-dose, high-dose group, and metformin group.After four weeks of intervention, fasting blood glucose ( FBG ) was measured; Morris water maze was used to detect spatial learning and memory ability in rats; Nissl staining and immunofluorescence staining were respectively used to detect the degree of brain injury and the expression of lba-1 , a marker of microglia .EL1SA was used to detect the expression of TNF-cx, IL6, ILK) and BDNF.Western blot was employed to detect the expression of JAK2/STAT3 pathway.Results Compared with the control group, the model group showed significant increase in blood glucose, decreased spatial learning and memory capacity, severely damaged hipp-ocampal neurons, increased activated microglia, significantly higher levels of TNF-cx, 1L6, p-JAK2/JAK2 and p-STAT3/STAT3, and signif icantly lower levels of ILK) and BDNF.Compared with the model group, QFY group effectively reduced FBG, inhibited the con-tinuous rise of FBG, improved learning and memory a- bility, improved hippocampal neuronal damage, reduced activated microglia, reduced TNF-cx, 1L6, p- JAK2/JAK2 and p-STAT3/STAT3 levels, and increased ILK) and BDNF levels.Conclusion QFY has been shown to improve type 2 diabetic cognitive impairment , and the mechanism may be related to the inhibition of blood glucose rise and regulation of the JAK2/STAT3 pathway, thereby inhibiting microglia activation.
RESUMO
Qifu-Yin (QFY), a widely used formula of traditional Chinese medicine (TCM) derived from "Jingyue Quanshu", is one of the most commonly used TCM prescriptions for the clinical treatment of Alzheimer disease. The role of advanced glycation end products (AGEs) and its receptor RAGE have attracted increasing attention as the pivotal role of Aβ has been questioned. The present study was designed to test the neuroprotective effects of QFY, and the possible mechanism in AGE-induced Alzheimer model rats. After injection of AGE in the CA3 area of the hippocampus, QFY (8.6, 4.3, and 2.15 g·kg(-1)), and a positive control drug donepezil (2 mg·kg(-1)) were administrated through gastric intubation to rats once daily for thirty consecutive days. Another positive control group was the AGE + anti-RAGE group, which was simultaneously injected with anti-RAGE antibody before AGE treatment. The control group, sham-operated group, as well as the AGE + anti-RAGE group received saline at the same dosage. The Morris water maze test and the step-down passive avoidance test were conducted to evaluate the cognitive function of the rats. The expression of RAGE and NF-κB were assayed by immunohistochemical staining. The levels of Aβ, TNF-α, and IL-1β in the hippocampus were measured by enzyme-linked immunosorbent assay (ELISA). The results showed that QFY could significantly attenuate the memory impairment induced by AGE, decrease the expressions of RAGE and NF-κB, and reduce the levels of Aβ, TNF-α, and IL-1β in the hippocampus in a dose-dependent manner. Also, the blockage of RAGE could significantly reduce the impairments caused by AGEs. In conclusion, QFY could attenuate AGEs-induced, Alzheimer-like pathophysiological changes. These neuroprotective effects might be related to the RAGE/NF-κB pathway and its anti-inflammatory activity.