Mitochondrial quality control includes mechanisms such as mitochondria-derived vesicles, fusion / fission and autophagy. These processes rely on the collaboration of a variety of key proteins in the inner and outer membranes of mitochondria to jointly regulate the morphological structure and functional integrity of mitochondria, repair mitochondrial damage, and maintain the homeostasis of their internal environment. The imbalance of mitochondrial quality control is associated with leukemia. Therefore, by exploring the mechanisms related to mitochondrial quality control of various leukemia cells and their interactions with immune cells and immune microenvironment, this article sought possible targets in the treatment of leukemia, providing new ideas for the immunotherapy of leukemia.
Objective To investigate the cell growth inhibition and apoptosis induced by rapamycin on human hepatocellular carcinoma Bel-7402 cells and to study the role of mitochondrium membrane potential in the process of apoptosis. Methods Bel-7402 cells in vitro were given 5, 10, 20, 30, 40 and 50 nmol/L different concentrations of rapamycin, and the cell growth inhibiting ratio of Bel-7402 was assessed by MTT assay. The changes of morphology of Bel-7402 were observed by Hoechst 33258 staining and flow cytometry (FCM), respectively; The cell mitochondrial membrane potential was detected by using JC-1 staining method. Results Rapamycin could inhibit the growth of Bel-7402 cells significantly by inducing apoptosis, and the growth suppression and the cell apoptosis both presented time-effect relationship and were also dose-dependent. The rates of inhibiting and cell apoptosis after 72 h exposure to 50 nmol/L rapamycin were significantly higher that those of other groups (P＜0.01). Typical morphological changes of cell apoptosis were observed very clearly after the Bel-7402 cells had been exposed to rapamycin for 48 hours using Hoechst 33258 staining method, and it was also observed that the mitochondrial membrane potential decreased when apoptosis occured (P＜0.01). Conclusion Rapamycin could inhibit the growth of Bel-7402 cells by inducing cell apoptosis, and the descent of mitochondrial membrane potential may play an important role in the process of cell apoptosis.
ObjectiveTo explore the relationship between mitochondrial function and the severity of sepsis by detecting the platelet mitochondrial permeability transition pore, transmembrane potential and adenosine triphosphate (ATP) levels in peripheral blood. MethodsAccording to random number table, 40 male SD rats were randomly divided into three sepsis model groups (group A, B and C) and a sham group (group D). The rats in the model groups received cecal ligation and puncture (CLP) treatment with different percent of ligated length in total length of the cecum (10% in group A, 30% in group B and 50% in group C, respectively). Twenty-four hours later, peripheral blood was collected for TNF-α, IL-1βand IL-6 levels determination, also the mitochondrial permeability transition pore, transmembrane potential and ATP content were tested in the isolated platelet. One-way ANOVA test was used to determine the relevance between above indices and the severity of sepsis. Meanwhile, 29 patients with sepsis were enrolled for clinical study. After APACHEⅡscoring, platelet samples of peripheral blood in the patients were collected for mitochondrial function determination. The relationship between mitonchondrial function and APACHEⅡscore was analyzed by Spearman method. ResultsCalcein fluorescence, membrane potential and ATP synthesis in platelet mitochondria of the rat sepsis model were gradually decreased with the increased severity of CLP, and the difference among these groups were all statistically significant (all P < 0.05). In clinical specimens, APACHEⅡscore was negatively correlated with ATP level of platelet mitochondria(r=-0.895, P < 0.05). ConclusionMitochondrial function of platelet in peripheral blood can be used as an effective indicator for the severity of sepsis.
目的:分析原发性胆汁性肝硬化(PBC)患者的临床表现,试验室检查及治疗情况。方法:回顾性分析48例PBC患者临床资料。结果:93.8%是中年女性患者,平均年龄53.2±8.73。主要的临床表现包括肝功能异常(ALT、GGT、AKP升高)95.8%,乏力纳差83.3%,黄疸79.2%,瘙痒66.6%,肝肿大62.5%,脾大58.3%等。常合并干燥综合征(25%),类风湿关节炎(16.7%)等自身免疫性疾病及结缔组织疾病。所以患者AMA及AMAM-2均为阳性。全部病例使用熊去氧胆酸治疗,但仅31.3%患者病情有不同程度好转。结论:加强对PBC的认识,重视对AMA 或AMA-M2的检测,尤其对长期不明原因肝功能异常的女性患者。
Objective\ To study the mechanism of myocardial protection of exogenous creatine phosphate (CP) against ischemia reperfused injury in modified isolated perfused working rat heart model.\ Methods\ Seventy two rats were divided into five groups.The rat hearts of five groups undergone Langendorff perfused were arrested and made totally ischemic for 40 minutes at 37℃ and reperfused for 20 minutes. St.Thomas cardioplegic solution wasn’t used in group A;It was used immediately after ischemia in group B and grou...
ObjectiveTo observe the clinical features of patients over 30 years old with Leber hereditary optic neuropathy (LHON). MethodsNine male LHON patients (18 eyes) were enrolled in this study. The patients aged from 34 to 56 years old, with an average age of (45.22±6.91) years. The course of the disease ranged from 7 days to 21 months, with a mean course of 5 months. Visual acuity, slit lamp microscope, chromoptometry, direct ophthalmoscope and fundus photography were measured for all patients, visual field examined for 6 patients (11 eyes). Mitochondrial DNA mutation was analyzed. The visual acuity was followed-up for 12 months. ResultsSeven of the 9 patients (77.78%) had family history. Five patients (55.56%) had both eyes involved simultaneously, and 4 patients (44.44%) had the eyes involved at different time. Three patients (33.33%) had sudden visual loss, and 6 patients (66.67%) had gradual visual loss. The visual acuity was light perception in 1 eye (5.55%), finger counting in 3 eyes (16.67%), 0.01-0.1 in 7 eyes (38.89%), 0.12-0.3 in 3 eyes (16.67%), equal or greater than 0.4 in 4 eyes (22.22%). Sixteen eyes (88.88%) had normal light reflex, 1 eye (5.55%) had no light reflex, and 1 eye (5.55%) had relative afferent papillary defect. Eight eyes (44.44%) had normal optic disk, 3 eyes (16.67%) had blurred optic disc border and disc telangiectasia, 7 eyes (38.89%) had pale disc and clear boundary. Among 11 eyes underwent visual field examination, 9 eyes (81.82%) had central or paracentral scotoma and 2 eyes (18.18%) had visual field narrowing. Among 9 patients, there were 7 patients (77.78%) with G11778A mutation, 1 patient (11.11%) with G11696A mutation, and 1 patient (11.11%) with T14484C mutation. In the last follow-up, the visual acuity was light perception in 1 eye (5.55%), finger counting in 4 eyes (22.22%), 0.01-0.1 in 6 eyes (33.33%), 0.12-0.3 in 3 eyes (16.67%), equal or greater than 0.4 in 4 eyes (22.22%).The visual acuity was improved in 9 eyes (50.00%), stable in 7 eyes(38.89%), and decreased in 2 eyes (11.11%). ConclusionLHON patients (older than 30 years) are more common in men, mostly with normal light reflex, central or paracentral scotoma and G11778A mutation.
Objective To investigate the effects of diazoxide （DIA）cardioplegic solution on the reduction of donor cardiomyocyte apoptosis, Methods In a Krebs-Henseleit （KH） solution perfused isolated rabbit heart Langendorff model, 32 rabbit hearts were divided into four groups with simple random sampling （8 rabbits in each group ）： DIA group （50μmol/L diazoxide mixed in KH solution）,STH group （ST, Thomas＇ solution）, 5-HD group （50μmol/L diazoxide and 100μmol/L 5-hydroxydecanoic acid mixed in KH solution）, KH group （KH solution）, The rabbit hearts of each group underwent 6 hours of hypothermic （4 C） storage in the corresponding cardioplegic solution. Left ventricular developed pressure （LVDP）, maximal values of positive rate of left ventricular pressure （＋dp/dtmax） were measured before and after storage, The post-storage values of LVDP and ＋dp/dtmax were expressed as the percentage of pre-storage control values. Apoptotic cardiomyocytes were detected by the TdT- mediated dUTP-biotin nick end labeling （TUNEL）. Malonaldehyde （MDA） contents and adenosine triphosphate （ATP） contents were also measured after storage. Results Recovery rates of LVDP, ＋dp/dtmax, and ATP contents in DIA group were higher than those of other 3 groups respectively（P〈0. 05）, Cardiomyocytes apoptosis percentage and MDA content were lower than other 3 groups respectively（P〈0. 05）, Conclusions Diazoxide cardioplegic solution can protect the isolated hearts and this may be relates to opening selective mitochondrial KATP channels. The selective mitochondrial KATP channel antagonist 5-hydroxydecanoic acid can block the cardioprotective effect of diazoxide.
Objective To investigate the major types and clinical manifestations of mitochondrial DNA (mtDNA)mutations in Chinese patients with Leber′s hereditary optic neuropathy(LHON). Methods A total of 119 patients with bilateral optic neuropathy from 117 pedigrees, including 37 with determinate diagnosis of LHON(group A) and 82 with suspected LHON(group B),were tested for mtDNA mutations by using single-strand conformational polymorphism, mutation-specific primer polymerase chain reaction and sequencing. Pertinent clinical data and history of the patients with the 11778 mutation were collected. Results Nucleotide positions(np)11778 mutation and np 14484 mutation was found in 33 (89.2%) and 3 (8.1%) patients respectively in group A, while np 11778 mutation was obtained in 26（31.7%）in group B. No 3460 mutation was found in group A or B. The clinical manifestations of 59 patients with np 11778 mutation were as follows: acute or chronic visual loss，no ophthalmalgia, the age of onset of 10-25, and either a central or paracentral scotoma in perimetry. The visual recovery rate was 8.6%～11.6%. Conclusion Chinese patients with LHON have a very high incidence of np 11778 mutation and the clinical manifestations of the patients with np 11778 mutation are similar to those of Caucasian patients. (Chin J Ocul Fundus Dis，2004，20：78-80)
Objective To investigate the changes in mitochondrial morphology, structure and function in rats with severe intermittent hypoxia, as well as the effects of intermittent hypoxia and its severity on cognitive function. Methods A total of 18 rats were selected to construct a model of severe intermittent hypoxia, which were divided into a normal control group, an intermittent air control group, and a 5% intermittent hypoxia group for 8 weeks, with 6 rats in each group. The structural and functional changes of mitochondria in the hippocampal CA1 region were observed. A total of 30 rats were randomly divided into 5 groups: a normal control group, an intermittent air control group, a 5% intermittent hypoxia 4-week group, a 5% intermittent hypoxia 6-week group, and a 5% intermittent hypoxia 8-week group, with 6 rats in each group. The cognitive function of the rats in each group was evaluated by Morris water maze experiment. Results In the mitochondria of the hippocampal CA1 region of severely intermittent hypoxic rats, bilayer membranes or multilayer membranes were visible, the mitochondria were swollen, cristae were broken and vacuolated, and their respiratory function was significantly weakened, the membrane permeability was increased, and the membrane potential was reduced. In the Morris water maze, there was no significant difference in swimming speed between the rats. With the prolongation of intermittent hypoxia action time, the latency of finding the hidden platform in each group of rats increased significantly, and the residence time of the target quadrant decreased significantly. Conclusions Mitochondrial structure in the hippocampal CA1 region of the rat brain is destroyed during severe intermittent hypoxia, and dysfunction and cognitive impairment occur. With the prolongation of intermittent hypoxic injury, the degree of cognitive impairment worsens.