1.Study of synergistic effect of hyperlipoproteinemiaand Aβ in processing of Alzheimer′s disease
Jiangqi HOU ; Xin ZHANG ; Qin LONG ; Shifeng CHU ; Lei GUO ; Wenbin HE ; Junlong ZHANG ; Naihong CHEN
Chinese Pharmacological Bulletin 2017;33(4):498-506
Aim To research the synergistic effect of hyperlipoproteinemia and Aβ in the processing of Alzheimer′s disease.Methods Seventy SD rats were randomly divided into seven groups, and dealt with D-gal(hypodermic injection), hyperlipemia diet, microinjection into both side of CA1 section in hippocampus, independently.Morris water maze(MWM) test was used to evaluate the spatial memory impairments.Tau and tau(pThr181) pathology in the hippocampus were detected using Western blot and immunohistochemistry.Nissl′s staining was used to detect cell apoptosis.Results Aβ25-35-treated rats showed significant impairments of spatial memory in MWM test, especially in the group of D-gal+Aβ25-35+HLD(P<0.01).Furthermore, these rats treated with Aβ25-35, D-gal, and hyperlipemia diet, exhibited significantly increased phosphorylation of tau, particularly in the Thr181 site.Conclusion Hyperlipoproteinemia is the risk factor for older person, which could strengthen the toxic effect of Aβ, and promote phosphorylation of tau.
2.Study on the specificity of Tau protein phosphorylation sites in three typical patterns of senile dementia based on the same disease with different patterns
Bin GUO ; Lei GUO ; Cheng HAN ; Yali QIN ; Weibin SHI ; Jiangqi HOU
Journal of Beijing University of Traditional Chinese Medicine 2017;40(6):492-497
Objective To observe Tau protein phosphorylation in rats with three typical patterns of senile dementia, analyzing and summarizing the specificity of phosphorylation.Methods We ligated and dissected the left and right carotid arteries at one week's interval with intraperitoneal injection of D-galactose to establish senile dementia model in rats.Those rats then received the intervention of excessive sexual and physical exertion, high-fat feeding milk and low temperature environment respectively to establish the rat models of senile dementia with three different patterns (group K: kidney deficiency and essence loss pattern;group P: retention of phlegm and turbid substance in orifices pattern;group C: congealing cold and blood stasis pattern).Blood lipid, blood rheology and serum testosterone were measured to identify whether those model was built successfully.Different positions of Tau phosphorylation sites were measured with Western blot method.Results In the Tau protein proline-rich region, compared with the diseased groups, phosphorylation level increased significantly at the sites of 205 and 231 in group P.This increase was also present at sites of 181, 205, and 231 in group K and 205, 231 and 262 in group C.At the C-terminal region, compared with the diseased group, phosphorylation level of P group and K group were significantly increased at the sites of 404, and the increase of group C was the highest among those groups.Conclusion There is specificity at the Tau protein phosphorylation sites in each typical senile dementia pattern.This study may reveal the scientific rationale for the presence of different patterns in the same disease.