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This study was aimed to observe the protection ofZi-Bu Pi-Yin recipe (ZBPYR) on the cortex mitochondrial dysfunction of diabetes-associated cognitive dysfunction rats. SD rats were randomly divided into four groups, which were the control (Con) group, the diabetes (DM) group, the ZBPYR treatment (ZBPYR1) group and the ZBPYR protection (ZBPYR2) group. Morris water maze test was taken to evaluate the learning and memory ability of rats. The transmission electron microscope (TEM) was used to detect the ultrastructure and quantity changes of cortex mitochondria. Western blot was used to detect the expression of Cyto C. The results showed that compared to Con group, the learning and memory ability were decreased in the DM group (P < 0.05); the learning and memory ability of the ZBPYR1 group was improved compared to the DM group (P < 0.05); compared to the DM group, the ZBPYR2 group was significantly improved (P < 0.01). Compared with the Con group, the number of cortex mitochondria in DM group was decreased (P< 0.05), and the structure was disordered, blurred, or even completely destroyed. After ZBPYR intervention, these pathological changes were reduced obviously. And the number of mitochondria in the ZBPYR2 group was increased than that of the DM group (P < 0.05). The expression of Cyto C in cytoplasm of the DM group was significantly higher than that of the Con group (P < 0.01). After ZBPYR intervention, the expression of Cyto C was decreased. It was concluded that ZBPYR regulated the mitochondrial morphology and changes of volume in the cortex, prevented the releasing of Cyto C from mitochondria to cytoplasm, and improved the cognitive function of diabetes rats.
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Objective To clarify the pathogenesis of spleen yin deficiency diabetes-associated cognitive decline (DACD) and mechanism of Zinu Piyin Recipe (ZBPYR) by observing the expression of phosphorylated RNA-dependent protein kinase-like endoplasmic reticulum kinase (PERK), eukaryotic initiation factor 2α subunit (eIF2α), p-eIF2α, glucose-regulated protein 78 (GRP78) in cerebral cortex of spleen yin deficiency diabetes mellitus rats. Methods The rats were randomly divided into control group, diabetes mellitus group, spleen yin deficiency group, spleen yin deficiency diabetes mellitus group (disease-syndrome group) and spleen yin deficiency diabetes mellitus+ZBPYR group (treatment group). Type 2 diabetes mellitus models were established by high-fat food feeding for 4 weeks and low dose STZ intraperitoneal injection. Then the classical compound method was used to construct spleen yin deficiency rats model by improper diet, over exertion and yin fluids exhaustion. The reatment group was given ZBPYR and other groups were given equal volume of normal saline for 15 days, then cerebral cortex was obtained. The expression of p-PERK, p-eIF2α, eIF2α and GRP78 were observed by Western Blot and RT-PCR. Results The protein expression of p-PERK, p-eIF2α, and mRNA expression of GRP78 of diabetes mellitus group, spleen yin deficiency group and disease-syndrome group was enhanced compared with control group (P<0.05). GRP78 protein expression of diabetes mellitus group, disease-syndrome group was increased compared with control group (P<0.05). The protein expression of p-PERK, p-eIF2α, GRP78 and mRNA expression of GRP78 of treatment group was decreased compared with diabetes mellitus group and disease-syndrome group (P<0.05). Conclusion Endoplasmic reticulum stress is involved in spleen yin deficiency DACD. ZBPYR improves learning and memory ability by reducing endoplasmic reticulum stress.
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This study was aimed to observe changes of key molecular in insulin signaling pathway in the hypothala-mus of rats to explore the mechanism of spleen yin deficiency diabetes-associated cognitive decline (DACD) and Zibu Piyin Recipe (ZBPYR) in order to provide new ideas and new clues for treatment of DACD. Rats were randomly divided into five groups, which were the control (Cont) group, diabetes (DM) group, spleen yin deficiency (pi) group, spleen yin deficiency diabetes (piDM) group and the ZBPYR group. Insulin receptor substrate 1 (IRS-1) serine phos-phorylation levels and protein kinase B (PKB/Akt) serine phosphorylation levels which were involved in the insulin signaling were observed by western blotting in the hypothalamus to determine whether there were insulin signaling obstacles in the hypothalamus of rats. The results showed that the expression of p-IRS-1ser in the DM group, pi group and piDM group was increased compared with the Cont group (P< 0.05); while the p-Akt expression of the DM group and piDM group was decreased (P< 0.05). The expression of p-IRS-1ser in the ZBPYR group decreased compared with the DM group and piDM group (P< 0.05); while the level of p-Akt increased compared with the DM group and piDM group (P < 0.05). It was concluded that insulin signaling was not transduced normally in the hy-pothalamus of the DM group, pi group and piDM group. Insulin resistance may occur in the hypothalamus. And ZBPYR can correct insulin signaling transduction disorder.
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Objective To explore the mechanism of Zibu Piyin Recipe (ZBPYR) on spleen yin deficiency diabetes-associated cognitive disorder (DACD). Methods The rats were randomly divided into control group, diabetes mellitus (DM) group, spleen yin deficiency group, spleen yin deficiency DM group and spleen yin deficiency DM+ZBPYR group (treatment group). Type 2 DM models were established by high-fat food feeding and low dose STZ intraperitoneal injection for 4 weeks. Then the classical compound method was used to construct spleen yin deficiency rat models by improper diet, over exertion and yin fluids exhaustion. The treatment group was given ZBPYR by gavage for 15 days, and the other groups were given the same amount of normal saline. Then cerebral cortex, hippocampus, stomach and liver were obtained and the changes of protein expression of PDHE1α in them were observed by Western Blot. Results The protein expression of PDHE1αin cortex of DM group and spleen yin deficiency DM group were lower than control group (P<0.05). PDHE1α expression of treatment group in cortex and stomach increased more significantly than spleen yin deficiency DM group (P<0.05). The expression of PDHE1α protein showed no significant difference among all groups in hippocampus and liver. Conclusion ZBPYR improved spleen yin deficiency DACD by regulating PDHE1αin cortex and stomach.
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This study was aimed to observe different forms of β-amyloid peptide (Aβ) and insulin degrading enzyme (IDE) in the hippocampus and cortex in order to further explore the role of Aβ and IDE on spleen yin deficiency di-abetes-associated cognitive decline (DACD), and the effect of Zi-Bu Pi-Y in method. The rats were randomly divided into five groups, which were the blank control (Cont) group, diabetes (DM) group, spleen yin deficiency (pi) group, spleen yin deficiency diabetes (piDM) group and Zi-Bu Pi-Y in recipe (ZBPYR) group. Soluble and insoluble Aβ in the hippocampus and cortex of rats were extracted by gradient centrifugation, and then measured by ELISA. The ex-pression of IDE was observed by western blot. The results showed that the content of soluble and insoluble Aβ1-42 in the hippocampus and cortex of the DM group and piDM group were higher than the Cont group. The soluble and in-soluble Aβ1-42 content in the hippocampus and cortex of the ZBPYR group were reduced compared with the DM group and the piDM group. The soluble Aβ1-40 in the cortex of the DM group, pi group and piDM group were in-creased compared with the Cont group (P < 0.05). The soluble Aβ1-40 content of the ZBPYR group was decreased compared with the DM group and the piDM group (P < 0.05). The expression of IDE protein was decreased in the hippocampus of the DM group and the piDM group compared with the Cont group (P< 0.05), and the IDE protein level in the hippocampus of the ZBPYR group was increased compared with the DM group and the piDM group (P<0.05). The expression of IDE protein in the cortex of the DM group, pi group and piDM group was lower than the Cont group (P< 0.05). The IDE protein level in the cortex of the ZBPYR group was reduced compared to the DM group (P< 0.05). It was concluded that the increased Aβ1-42 in brain may be a major pathological change of DACD and spleen yin deficiency DACD. The decreased IDE expression may be one of the reasons to induce increasing of Aβ1-42 level. The Zi-Bu Pi-Y in method may decrease the Aβ1-42 content by upregulating IDE protein expression.
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Objective To investigate expression changes of Tau protein in retinal ganglion cells (RGCs) and oligodendrocytes (Ols) after stretch injury in rats and explore the relationship of Tau protein with pathological changes after axonal injury. Methods Morphological changes of optic nerves, RGCs and OLs after stretch injury were examined under light microscope in control group, stretch only group, heat stress only group and heat stress pretreatment plus stretch group. The expressions of Tau protein in RGCs and OLs after heat stress and/or stretch injury were observed by using immunohistechemical stai-ning. Results Pathological changes of axons, RGCs and OLs were identified morphologically or quan-titatively after stretch injury to the optic nerves, which was significantly ameliorated through pretreatment with heat stress plus stretch injury. The expressions of Tau protein in RGCs and OLs were increased in stretch only group. There was no significant expression change of Tau protein in heat stress only group. Expression of Tan protein was obviously decreased in heat stress pretreatment plus stretch group. Con-clusions Both neurons and glial cells are involved in pathological process after axonal injury. The ex-pression changes of Tau protein are probably related to delayed axotomy and neuron apoptosis. Heat stress can relieve the impairment of cystoskeleton through decreasing and delaying the expression of Tau protein.
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BACKGROUND: At present, traditional modalities of neuroimaging, such as CT and MRI, is very limited in the diagnosis and severity estimation of diffuse axonal injury (DAI).OBJECTIVE: To investigate the value of proton magnetic resonance spectroscopy (1HMRS) in the diagnosis and prognosis of DAI.DESIGN, TIME AND SETTING: Prospective clinical controlled observation. The study was performed at the Department of Neurosurgery, and Department of Radiology, First Affiliated Hospital of Chongqing Medical University between October 2002 and September 2007.PARTICIPANTS: A total of 63 subjects with traumatic brain injury were enrolled and divided into DAI group (n=27) and non-DAI group (n=36) according to the result of MRI. In addition, 20 healthy persons were served as control group.METHODS: Demographic and clinical data were recorded on admission and neuroimaging examinations including fluid attenuated inversion recovery were carried on according to carefully designed procedures, in addition, 1HMRS was performed and the data were analyzed in combination with clinical condition.MAIN OUTCOME MEASURES: The ratios of N-acetyl aspartate (NAA)/creatine (Cr) and creatine phosphate (Cr), Choline compound (Cho)/Cr, myoinositol (mlNs)/Cr, and glutamic acid (GIx)/Cr at genu and splenium of corpus cellosum, and basal ganglia were quantified using 1HMRS.RESULTS: Compared with control and non-DAI groups, DAI group had decreased NAA/Cr and increased Cho/Cr at genu and splenium of corpus callosum, and basal ganglia (P < 0.05- 0.01), as well as increased mlNs/Cr and Glx/Cr at genu and splenium of corpus cellosum (P < 0.05). Non-DAI group also showed decreased NAA/Cr at splenium and increased Cho/Cr at genu of corpus callosum compared with control group (P < 0.01), but the change degree was less than DAI group. A positive correlation between Cho/Cr at genu of corpus callosum and the peded of primary unconsciousness was identified in DAI group (r=0.824, P < 0.01). CONCLUSION: The 1HMRS indexes at genu and splenium of corpus callosum, and basal ganglia could serve as effective indexes for the diagnosis of DAI. The Cho/Cr could well reflect histological changes following injury and act as sensitive index to predict clinical injury.
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Objective To observe the expression of interleukin-1β (IL-1β) in blood serum after axonal injury in rats and investigate the effects of ciclosporin A (CsA) on it so as to discuss mechanism of CsA protecting neural function. Methods A total of 75 adult male SD rats were randomly divided into control group (Group A with 5 rats), only optic nerve stretch group (Group B with 35 rats) and stretch plus CsA treatment group (Group C with 35 rats). Stretch injury was induced in the right optic nerves of the rats in Group B and C. CsA at 20 mg/L was intraperitonealy injected in Group C immediately after stretch injury. Five animals from both Group B and Group C were killed at 1,3, 6, 12 hours and at days 1,3 and 7 after stretch injury or injection of CsA respectively. Morphological changes of optic nerves and retinal ganglion cells (RGCs) after stretch injury were examined under light microscope. In the mean- time, expression of IL-1β in the blood serum was observed by means of radioimmunoassay. Results (1) Histopathological observation showed lose of R GCs at day 3 and disarranged nerve fiber at day 7 after stretch injury of optic nerve in Group B, but significant amelioration of corresponding changes in Group C. (2) The expression of IL-1β in blood serum in Group B was significantly higher than that in Group A 3, 6, 12 hours and 1 day after injury. The expression of IL-1β reached peak at the 6th hour, then de- creased gradually and returned to the similar level of Group A after 3 days. The expression pattem of IL- 1 β in blood serum of Group C decreased more significantly at 3, 6, 12 hours and 1 day compared with that in Group B but was still higher than that of Group A at 6, 12 hours and 1 day. Conclusions The long-term and excessive expression of IL-1β may be involved in the secondary pathological changes after axonal injury. CsA exerts neuroprotective effect on injured axons mostly by attenuation of inflammation re- action after axonal injury.
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Objective To explore the microsurgical technique in managing medial sphenoid ridge meningioma.Methods The clinical data of 23 cases of medial sphenoidal ridge meningioma were analyzed retrospectively.The main points of microsurgical treatment of medial sphenoid ridge meningioma were discussed.Results Of 23 cases of medial sphenoid ridge meningiomas,total removal was made in 15 cases,subtotal removal in 6 cases and partial removal in 2 cases.The microsurgical outcomes were satisfactory in all the patients and no patients died.Conclusion The microsurgery via the pterional approach to the medial sphenoid ridge meningiomas can greatly heighten total resection rate of the tumors.Total resection of the tumor depends on its position,character and degree of edema of surrounding tissues.Palliative operations combined with postoperative radiotherapy should be carried out for treating the tumors that can only be subtotally and partially removed.
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Objective To explore the relationship between mRNA and protein expressions of PTTG, bFGF, P53 with tumorigenesis and invasiveness of pituitary adenoma. Methods The protein expressions of PTTG, bFGF, P53 were detected by immunohistochemical analysis, and their mRNA expressions were by reverse transcription polymerase chain reaction (RT-PCR) in 63 specimens of pituitary adenoma that was classified into invasive and non-invasive according to Wilson’s modified staging. Results Thirty-four specimens of pituitary adenoma were invasive and 29 non-invasive. The expressions of PTTG, bFGF, P53 were significantly higher in invasive pituitary adenoma than in non-invasive. The analysis of correlation showed that in invasive pituitary adenoma, the positive correlation exists between PTTG and bFGF mRNA (r=0.81, P
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Objective To explore the efficiency,safety and suitable dosage of the non-invasive treatment of malignant gliomas with high intensity focused ultrasound(HIFU).Methods An extracorporeal HIFU with 9.7 MHz transducer(focal length: 4.5 mm,focal intensity: 2 500 W/cm~(2)) was used.Fifteen resected human malignant gliomas were randomly assigned to receive HIFU ablation for 10,20,30 s.After the treatment,the exposure coverage and marginal zone were collected and examined by HE staining and electron microscope.Results Exposure coverage and margin was safe in 10 s group.Typical coagulation necrosis was detected at exposure coverage with no detectable change at margin in 20 s group.Typical coagulation necrosis was seen at both exposure coverage and margin in 30 s group.Conclusion Under the parameters used in this study,20 s is a beneficial therapeutic dosage.HIFU is an accurate method for malignant gliomas ablation.
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<p><b>OBJECTIVE</b>To investigate the effect of moderate hypothermia on responses of axonal cytoskeleton to axonal injury in the acute stage of injury.</p><p><b>METHODS</b>Of fifteen adult guinea pigs, twelve animals were subjected to stretch injury to the right optic nerves and divided into the normothermic group (n = 6) in which the animal's core temperature was maintained at 36.0-37.5 degrees C and the hypothermia group (n = 6) in which the core temperature was reduced to 32.0-32.5 degrees C after stretch injury. Remaining three animals sustained no injury to the right optic nerves and served as control group. Half of injured animals (n = 3) of either normothermic group or hypothermic group were killed at either 2 hours or 4 hours after injury. The ultrastructural changes of axonal cytoskeleton of the right optic nerve fibers from the animals were examined under a transmission electron microscope and analyzed by quantitative analysis with a computer image analysis system.</p><p><b>RESULTS</b>At 2 hours after stretch injury, there was a significant reduction in the mean number of microtubules (P < 0.001), and a significant increase in the mean intermicrotubule spacing (P < 0.05 or P < 0.01) in axons of all sizes in normothermic animals. The mean number of neurofilaments also decreased statistically (P < 0.01) in large and medium subgroups of axons in the same experimental group at 2 hours. By 4 hours, the large subgroup of axons in normothermic animals still demonstrated a significant decline in the mean number of microtubules (P < 0.01) and an increase in the mean intermicrotubule spacing (P < 0.05), while the medium and small subgroups of axons displayed a significant increase in the mean number of neurofilaments (P < 0.05) and reduction in the mean interneurofilament spacing (P < 0.05). On the contrary, either the mean number of microtubules and the mean intermicrotubule spacing, or the mean number of neurofilaments and interneurofilament spacing in axons of all sizes in hypothermic stretch-injured animals was not significant different from the mean values of sham-operated animals.</p><p><b>CONCLUSIONS</b>Posttraumatic moderate hypothermia induced immediately after axonal injury results in substantial protection of axonal cytoskeleton and ameliorates axonal damage.</p>
Subject(s)
Animals , Male , Axons , Pathology , Culture Techniques , Diffuse Axonal Injury , Pathology , Therapeutics , Disease Models, Animal , Guinea Pigs , Hypothermia, Induced , Methods , Microscopy, Electron , Optic Nerve , Pathology , Optic Nerve Injuries , Therapeutics , Probability , Random Allocation , Reference ValuesABSTRACT
Objective To investigate the clinical characteristics,diagnosis and treatment of invasive pituitary adenoma.Methods The clinical presentations,imaging studies and surgical outcomes in 62 patients with invasive pituitary adenomas and 78 patients with noninvasive pituitary adenomas were analyzed retrospectively.Results Invasive pituitary adenomas were more common in patients with macroadenomas than those with microadenomas(P