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Objective:To investigate the protective effect of endurance training on Parkinson disease(PD) mice and the effect of AMPK/mTOR pathway on autophagy and exosomes secretion.Methods:Thirty-two 10-week-old male C57BL/6 mice were randomly divided into quiet group, exercise group, PD quiet group and PD exercise group, with 8 mice in each group.The mice in exercise group and PD exercise group received 4-week treadmill endurance training.After training, mice in PD quiet group and PD exercise group were given rotenone (30 mg·kg -1·d -1) dissolved in 0.5% carboxymethyl cellulose salt solution and gavaged for 56 consecutive days.The mice in quiet group and exercise group were given 0.5% carboxymethyl cellulose salt solution by gavage.Then, the mice in exercise group and PD exercise group received treadmill endurance training for 4 weeks.The behaviors of mice in each group were measured after training.The content of tyrosine hydroxylase (TH) in substantia nigra of mice in each group was measured by immunohistochemistry.Western blot was used to detect the expression of plasma α-synuclein(α-syn), exosomes surface marker proteins CD9 and CD63, and the content of microtubule associated protein light chain 3-Ⅱ (LC3-Ⅱ), α-syn, adenine ribonucleotide dependent protein kinase (AMPK) and phosphorylated AMPK (p-AMPK), mammalian target of rapamycin (mTOR) and phosphorylated mTOR (p-mTOR) in substantia nigra of mice in each group.SPSS 20.0 software was used to analyze the data.One-way ANOVA was used for comparison among multiple groups and the LSD method was used for further pairwise comparison. Results:There was significant difference in the residence time of mice in the four groups on the rotarod instrument ( F=2 618.20, P<0.01). Compared with the quiet group, the residence time of PD quiet group decreased ((110.34±8.20) s, (186.20±6.83) s, P<0.01). Compared with the PD quiet group, the residence time of PD exercise group increased ((160.56±8.30)s, P<0.01). (2) There was no significant difference in the expression of plasma exosome marker proteins CD9 and CD63 among the four groups ( F=1.57, 1.26, both P>0.05). (3) There was significant difference in the expression of α-syn in plasma exosomes of the four groups ( F=1 303.99, P<0.01). The expression of α-syn in plasma exosomes in PD quiet group was higher than that of quiet group ((180.57±8.20), (100.00±0.00), P<0.01). Compared with the PD quiet group, the expression of α-syn in plasma exosomes in PD exercise group decreased ((150.23±7.30), P<0.01). (4) There was significant difference in the number of TH positive neurons in substantia nigra among the four groups ( F=447.09, P<0.01). Compared with the quiet group, the number of TH positive neurons in the substantia nigra of PD quiet group decreased ((48.23±6.30), (100.00±0.00), P<0.01). Compared with the PD quiet group, the number of TH positive neurons in the substantia nigra of PD exercise group increased ((68.62±8.20), P<0.01). (5) Western blot showed that there were significant differences in the expression of α-syn, p-mTOR, p-AMPK and LC3-Ⅱ in substantia nigra of the four groups ( F=753.62, 361.48, 261.95, 248.07, all P<0.01). Compared with the quiet group, the expression of α-syn in substantia nigra of PD quiet group increased ((184.16±15.31), (100.00±0.00), P<0.01), the expression of p-mTOR in substantia nigra increased ((156.77±3.99), (100.00±0.00), P<0.01), the expression of p-AMPK decreased ((70.65±8.43), (100.00±0.00), P<0.01), and the expression of LC3-Ⅱ in substantia nigra decreased ((72.25±7.86), (100.00±0.00), P<0.01). Compared with PD quiet group, the expression of α-syn in substantia nigra decreased ((158.23±9.30), P<0.01), the expression of p-mTOR in substantia nigra decreased ((123.61±16.86), P<0.01), the expression of p-AMPK increased ((96.35±9.45), P<0.01), and the expression of LC3-Ⅱ in substantia nigra increased ((108.89±10.67), P<0.01). Conclusion:Endurance training regulates autophagy and the expression of exosomes in PD mice through AMPK/mTOR signal pathway, protects dopaminergic neurons in mouse midbrain and improves motor function.
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Objective To investigate the effects of α-lipoic acid(ALA)on 6-hydroxydopamine(6-OHDA)-induced autophagy in human neuroblastoma(SH-SYSY)cells and its possible mechanisms.Methods SH-SYSY cells were divided into 5 groups:blank control group (group A),ALA group (group B),6-OHDA group(group C),ALA+6-OHDA group(group D),and rapamycin(RAPA)group (group E).The cell viability,cell apoptosis,and oxidative stress were assayed and analyzed in A-D group.The expression of autophagy-related proteins LC3-Ⅱ,AMP-activated protein kinase(AMP-K),phosphorylated AMPK (p-AMPK),the mammalian target of rapamycin (mTOR) and p-mTOR were detected by Western blot in A-E group.Results Compared with the blank control group,the 6-OHDA group significantly reduced the cell viability(P ＜ 0.01) and p-mTOR protein expression (P ＜0.05),and increased the cellular apoptosis rate(P＜0.01),oxidative stress level(P ＜0.01),LC3-Ⅱ protein expression(P＜0.05,with the highest level at 6 h after treatment),and p-AMPK protein expression(P＜＜0.05).There was no significant difference in these indices between ALA group and the blank control group.Compared with 6-OHDA group,ALA+ 6-OHDA group showed that the cell viability(P ＜ 0.01) and p-mTOR protein expression (P ＜ 0.05) were increased,while the cellular apoptosis rate(P＜0.01),oxidative stress level(P＜0.01),LC3-Ⅱ protein expression(P ＜0.05),and p-AMPK protein expression (P ＜ 0.05)were decreased.Conclusions The 6-OHDA can induce oxidative stress and autophagy in SH-SY5Y cells and decrease the cell viability.ALA can alleviate the 6-OHDA-induced cell injury possibly by inhibiting autophagy via AMPK/mTOR pathway.
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Objective To study causes of deterioration of sudden mydriasis in craniocerebral trauma patients with normal intracranial pressure and verify the efficiency of specific treatments.Methods A retrospective analysis was performed on causes of four cases of accidental mydriasis in normal intracranial pressure among 473 cases of craniocerebral trauma treated from June 2008 to March 2012.Changes of patients' condition and monitoring indices were observed after specific treatments.Results Abnormal mydriasis with synchronously normal intracranial pressure was largely due to sufficient decompression after a certain period of intracranial hypertension and persistence of brain perfusion pressure to more than 110 mm Hg or due to high cerebral perfusion pressure caused by redundant drainage of cerebrospinal fluid or low intracranial pressure (＜ 10 mm Hg),together with factors like low plasma osmotic pressure and carbon dioxide accumulation.The study showed that the intracranial pressure was maintained normal,that the brain swelling took a turn for better,that medical condition were stabilized and that pupil returned to normal in the four cases after treatment with specific protocol.GOS was four points in three cases and five points in one during follow-up at six months postoperatively.Conclusion Incidence of mydriasis with normal intracranial pressure in craniocerebral trauma patients can be efficiently declined through reduction of peripheral blood pressure,perfusion pressure controlling,hypertonic remedy maintenance and brain edema relief.
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Objective:To study the clinical benefit of propofol anesthesia with target-controlled influsion technic modulated by cerebral state index in the elderly patients with tumor. Methods:A total of 126 ASA Ⅰ or Ⅱ aged65 yrs or older patients underwent gastrectomy and rectal surgery were randomly divided into tow groups(n=63 each):group by target-controlled influsion technic modulated(groupⅠ)and group by target-controlled influsion(groupⅡ). CSI of groupⅠwas 50. Propofol of two groups was administered by TCI at a target blood concertration of 2?g/ml during induction of anesthesia and maintenance of anesthesia,sufentanil of two groups was administered by TCI at a target blood concertration of 1.5?g/ml during induction of anesthesia and of 0.3ng/ml during maintenance of anesthesia. MAP,HR,HRV and CSI of the foundation(T1),intubation(T2),five minutes after intubation(T3),chip(T4),the tumor excision(T5) and the end of surgery(T6) were recorded. And the total of propofol was recorded. Results:MAP at T3,T4 and T5 of groupⅡdecreased obviously compared to that of groupⅠ(P
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0.05),but the total of propofol was different(P