ABSTRACT
Diabetic peripheral neuropathy（DPN） is a neurodegenerative disease of diabetes mellitus involving peripheral nervous system damage， which is characterized by axonal degenerative necrosis， Schwann cell apoptosis and demyelination of nerve myelin sheath as the main pathological features， this disease is highly prevalent and is a major cause of disability in diabetic patients. Currently， the pathogenesis of DPN may be related to oxidative stress， inflammatory response， metabolic abnormality， and microcirculation disorder. The treatment of DPN in modern medicine mainly starts from controlling blood glucose， nourishing nerves and improving microcirculation， which can only alleviate the clinical symptoms of patients， and it is difficult to fundamentally improve the pathological damage of peripheral nerves. Mitochondrial quality control refers to the physiological mechanisms that can maintain the morphology and functional homeostasis of mitochondria， including mitochondrial biogenesis， mitochondrial dynamics， mitochondrial oxidative stress and mitochondrial autophagy， and abnormal changes of which may cause damage to peripheral nerves. After reviewing the literature， it was found that traditional Chinese medicine（TCM） can improve the low level of mitochondrial biogenesis in DPN， maintain the balance of mitochondrial dynamics， inhibit mitochondrial oxidative stress and mitochondrial autophagy， and delay apoptosis of Schwann cells and neural axon damage， which has obvious effects on the treatment of DPN. With the deepening of research， mitochondrial quality control may become one of the potential targets for the research of new anti-DPN drugs， therefore， this paper summarized the research progress of TCM in treating DPN based on four aspects of mitochondrial quality control， with the aim of providing a theoretical research basis for the discovery of new drugs.
ABSTRACT
Anesthesia is indispensable for surgere, but a growing number of studies have confirmed its togic effects on the developing nervous sestem, and has attract increasing attentions from the scientific communite. In this review, we briefle introduce the preclinical and clinical studies on the neurotogic effects of anesthetic drugs on the developing brain, and summare the mechanisms from the aspects of molecular mechanisms (Ca
ABSTRACT
Objective:To evaluate the role of Toll-like receptor 4(TLR4)/Src signaling pathway in activation of nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasomes in hippocampus in a rat model of hepatic ischemia-reperfusion (I/R).Methods:Thirty-two clean-grade healthy Sprague-Dawley rats, aged 8 weeks, weighing 200 g, were divided into 4 groups ( n=8 each) using a random number table method: sham operation group (Sham group), hepatic I/R group (HIR group), Toll-like receptor 4 (TLR4) inhibitor TAK-242 treatment group (TAK-242 group), and Src inhibitor PP2 treatment group (PP2 group). Hepatic I/R model was established by clamping hepatic vessels for 1.5 h followed by reperfusion in anesthetized rats.TAK-242 0.5 mg/kg was injected via the tail vein at 30 min before establishing the model in group TAK-242.PP2 0.03 mg/kg was intraperitoneally injected for 3 consecutive days before establishing the model in group PP2.The animals were sacrificed at 6 h of reperfusion, and hippocampal tissues were extracted for determination of interleukin-1β (IL-1β) and interleukin-18 (IL-18) contents (by enzyme-linked immunosorbent assay), malondialdehyde (MDA) content (by TBA method), superoxide dismutase (SOD) activity (using total superoxide dismutase assay), and expression of NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), c-Src, pro caspase-1, cleaved caspase-1, TLR4 and phosphorylated Src (p-Src) (Western blot). Results:Compared with Sham group, the contents of IL-1β, IL-18 and MDA were significantly increased, the SOD activity was decreased, and the expression of NLRP3, cleaved caspase-1, ASC, TLR4 and p-Src was up-regulated in the other three groups ( P<0.05). Compared with HIR group, the contents of IL-1β, IL-18 and MDA were significantly decreased, the SOD activity was increased, and the expression of NLRP3, cleaved caspase-1, ASC, TLR4 and p-Src was down-regulated in TAK-242 group and PP2 group ( P<0.05). There was no significant difference in each index between TAK-242 group and PP2 group ( P>0.05). Conclusion:The mechanism underlying activation of NLRP3 inflammasomes in hippocampus is related to activating TLR4/Src signaling pathway in a rat model of hepatic I/R.