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Effection of Catalpol on Diabetes-induced Learning and Memory Impairment in Rats

Author: RenLiZuo
Tutor: DuJianLing
School: Dalian Medical University
Course: Internal Medicine
Keywords: Catalpol Diabetic central nervous system disease Morris water maze Caveolin ( Cav - 1 ) Protein kinase C (PKC)
CLC: R587.2;R747.9
Type: Master's thesis
Year: 2008
Downloads: 129
Quote: 1
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Abstract


Background and Objective: diabetic encephalopathy (Diabetic encephalopathy) is based on learning and memory impairment as the main feature of the chronic complications of diabetes, its pathogenesis is not clear. Oxidative stress as a research hotspot in recent years doctrine with diabetes encephalopathy development are closely related. The Chinese medicine active monomer catalpol of (Catalpol) has been shown to have antioxidant, improve the role of ischemic neuronal injury, but its role in the prevention and treatment of diabetic encephalopathy has not been reported. The purpose of this study is to explore catalpol ability to antagonize the level of oxidative stress in the hippocampus of diabetic rats, regulation of protein caveolin -1 (Caveolin-1, Cav-1) and protein kinase Cγ subtypes (protein kinase C gamma, PKCγ) expression to improve learning and memory in rats, thus contributing to the in-depth understanding of the pathogenesis of diabetic encephalopathy provide a theoretical basis for the research and development of new drug clinical treatment of diabetic encephalopathy. Methods: 50 healthy male Sprague-Dawley (SD) rats were randomly divided into normal control group (NC group, n = 8), diabetic control group (DM group, n = 14), diabetes lipoic acid (DL-a- lipoic Acid ALA) intervention group (DL group, n = 14), the diabetes catalpol intervention group (DZ group, n = 14). DM group, DL group and DZ group established by intraperitoneal injection (50mg/kg body weight) in the streptozotocin (streptozotocin, STZ) diabetic rat model. 11 to 12 weeks after the animal into a mold, DL intraperitoneal injection of ALA (100 mg / kg body weight), DZ intraperitoneal injection Catalpol (5mg/kg body mass), once a day, a total of two weeks. The point of the 12 weeks the rats Morris water maze, recorded escape latency (s) and swam the distance (cm) was used to detect changes in the learning and memory ability. Thereafter the rats were killed, rapidly removed intact bilateral hippocampal tissue for HE sections staining, the determination of the level of oxidative stress, Total RNA was extracted conduct CAV-1, the PKCγ gene reverse transcription - polymerase chain reaction (reverse transcription -polymerase chain reaction, RT-PCR), and Cav-1 and PKCγ expression detected by Western blotting (Western blot). Results: (1) Morris water maze test: experiment the next day to the fifth day, the DM group compared with NC group escape latency and swim distance was significantly longer (P lt; 0.05, P lt; 0.01); DL group and DZ group. escape latency and swim out from the DM group was significantly shorter (P lt; 0.05, P lt; 0.01); DL groups and DZ group was no significant difference (P gt; 0.05) (2) HE staining of the hippocampus: NC hippocampal CA1 region of normal nerve cell morphology, structural integrity, arranged in neat rows; the DM cells disorganized, cell body shrink significantly reduced the number of red stained cytoplasm of morphologically normal cells; DL and DZ group cell morphology than normal, arranged in order, the structure is more complete. 3 hippocampal oxidative stress indicators: DM hippocampus malondialdehyde (malonaldehyde, MDA) content (the nmol / mgprot) (18.54 ± 2.32) compared with NC group (12.65 ± 1.09) was significantly higher (P lt; 0.01), DL group and DZ content of MDA were 14.66 ± 1.19 and 15.09 ± 1.11 were higher than those in NC group (P lt; 0.05) but significantly lower than the DM group (P lt; 0.01), DL group and DZ group was no significant difference (P GT ; 0.05). DM hippocampus reduced glutathione (reduced Glutathione, GSH) content (nmol / mgprot) (134.67 ± 11.82) than the NC group (194.48 ± 18.90) was significantly lower (P lt; 0.01), the the DL group of GSH content (177.76 ± 20.15) was significantly higher than DM group (P lt; 0.01), with the NC group, there was no significant difference (P gt; 0.05), DZ group of GSH (168.47 ± 21.55) lower than that in NC group (P lt; 0.05) but significantly higher DM group (P lt; 0.05), DL group and DZ group had no significant difference (P gt; 0.05). RT-PCR: DM group, the DL group and DZ group Cav-1 mRNA expression in hippocampal CA1 region compared with the NC group decreased significantly (P lt; 0.01), DL group and DZ group was significantly higher than DM group ( P lt; 0.05), DL group and DZ group difference was not statistically significant (P gt; 0.05) The DM group PKCγmRNA of expression than NC group was significantly lower (P lt; 0.01), the amount of DL group and DZ group was lower than that in NC group (P lt; 0.05) but significantly higher than DM group (P lt; 0.05), DL group and the DZ group difference was not statistically significant (P gt; 0.05) Western blot: DM group hippocampus Cav-1 protein expression compared with NC group was significantly lower (P lt; 0.01); DZ group compared with NC group (P lt; 0.05), but higher than the DM group (P lt; 0.05); DL group expression levels higher than the DM group, DZ group had no significant difference (P GT with NC group; 0.05) DM hippocampal PKCγ protein expression was significantly lower than the NC group (P lt; 0.01); DL group and DZ group expression were lower than NC group (P lt; 0.05), but significantly higher than DM group (P lt ; 0.01); DL group and DZ group difference was not statistically significant (P gt; 0.05) Conclusion: 1.12 weeks DM learning and memory in rats decreased significantly associated with hippocampal tissue morphology change, the degree of oxidative stress significantly increased Cav-1 and PKCγ expression to reduce the. Catalpol by upregulating the diabetic rat the hippocampus tissue expression of Cav-1 and PKCγ antagonistic oxidative stress, improve hippocampus morphological changes, to improve their learning and memory abilities, and thus play a protection role of the central nervous system.

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