Background: Emerging evidence suggests that chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect of chemotherapeutic drugs. Many experiments have proved that sodium aescinate (SA) has definit...Background: Emerging evidence suggests that chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect of chemotherapeutic drugs. Many experiments have proved that sodium aescinate (SA) has definite pharmacological effects such as anti-infection, anti-exudation, anti-edema, anti-tumor as well as neuroprotection, and the drug side effects are mild. However, no study has explored whether SA is involved in the analgesic effect of paclitaxel (PAC) induced neuropathic pain in rats. Methods: Rats were given an intraperitoneal injection of PAC (2.5 mg/Kg intraperitoneally on days 1, 3, 5, and 7), while SA 25 mg/kg intraperitoneally was administered daily for 14 consecutive days. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) of rats were examined on experimental days 3, 5, 7, 11, 14. All rats were sacrificed on day 15 of the experiment, and L4-6 spinal cords were removed. Subsequently, immunohistochemistry, HE staining, ELISA, RT-qPCR, Western blotting were applied to evaluate cytoskeletal protein expression (NF-L and NF-M), spinal nerve structural integrity, proinflammatory factor contents (TNF-α, IL-1β, and IL-6), and protein content of the TLR4/NF-κB pathway, respectively. Results: After the rats developed PAC induced pain behaviors, multiple injections of SA rendered the rats with elevated MWT and TWL values, decreased expression of NF-L and NF-M in the spinal cord, materially downregulated content of proinflammatory factors, and reduced amounts of TLR4 and p-NF-κB protein levels. Conclusions: The results of the present study preliminarily indicate that SA has an analgesic effect on rats with CIPN induced by PAC injection, and the mechanism may be related to blocking the TLR4/NF-κB signaling pathway, inhibiting the expression of proinflammatory factors, and alleviating cytoskeletal disorders.展开更多
Objective: When nerve injury or inflammatory injury, different miRNA-mediated signal pathways are activated or inactivated, causing pain or hyperalgesia. Therefore, miRNA has become a new direction of pain mechanism r...Objective: When nerve injury or inflammatory injury, different miRNA-mediated signal pathways are activated or inactivated, causing pain or hyperalgesia. Therefore, miRNA has become a new direction of pain mechanism research. We aimed to investigate the effect and mechanism of miR-362-3p on neuropathic pain in rats with chronic sciatic nerve injury (CCI). Methods: Neuropathic pain CCI rat model was established. Real-time-quantitative polymerase chain reaction (RT-PCR), Western blot, immunofluorescence, intrathecal injection, Enzyme-linked immunosorbent assay (ELISA), and dual luciferase reporter gene assays were used to explore the role of miR-362-3p in neuropathic pain development and the relationship between miR-362-3p and JMJD1A (Jumonji domain-containing 1A). Results: In the CCI group, the miR-362-3p level was increased and JMJD1A level was reduced in spinal cords and isolated microglia. The paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) values were increased, the secretion of inflammatory factors was reduced, and the microglial marker Iba1 expression was decreased after intrathecal administration of miR-362-3p. miR-362-3p was observed to target JMJD1A. JMJD1A elevation abolished the inhibitory effects of miR-362-3p on neuropathic pain development. Conclusion: Intrathecal administration of miR-362-3p significantly relieved neuropathic pain in CCI rats and inhibited neuroinflammation possibly through regulating JMJD1A.展开更多
Purpose: This research evaluates the efficacy of astaxanthin (AX) on cerebral ischemia/reperfusion (I/R) injury in rats and elucidates the potential mechanism of its neuronal protective effect. Methods: Rats were subj...Purpose: This research evaluates the efficacy of astaxanthin (AX) on cerebral ischemia/reperfusion (I/R) injury in rats and elucidates the potential mechanism of its neuronal protective effect. Methods: Rats were subjected to a middle cerebral artery occlusion/reperfusion (MCAO/R) model. Fifty grown male Sprague-Dawley (SD) rats were divided into 5 groups, including sham operation group (Sham), MCAO/R group, MCAO/R+AX group, MCAO/R+ AX+ Scramble group and MCAO/R+AX+ si-PPAR-γ group. The neurological score and cerebral infarction volume were evaluated after surgery. Rat microglia (RM) were stimulated by lipopolysaccharide (LPS) to form an inflammatory environment. LPS-induced RM cells were incubated with different concentrations of AX (1, 5 or 10 μg/mL), then cell viability, the expression of microglial activation markers, including cytokines (IL-1β, IL-6 and TNF-α), cluster of differentiation 68 (CD68), inducible nitric oxide synthase (iNOS) and CD206 and the expression of PPAR-γ and phosphorylated P65 (p-P65) proteins were determined. Cells were treated with pcDNA-PPAR-γ, as well as treatment with si-PPAR-γ or PPAR-γ antagonist GW9662 before AX treatment, and then cell activation mediators were tested. Results: AX inhibits LPS-induced RM cells activation and enhanced the expression level of PPAR-γ protein in way of dose-dependent, and pcDNA-PPAR-γ treatment had the same effect as AX. While si-PPAR-γ transfection or PPAR-γ suppressant GW9662 treatment reversed the effect of AX, and cut down the level of PPAR-γ protein and augmented the level of p-P65 protein. In addition, AX treatment alleviated the infarct volume, and sensorimotor and cognitive functions of MCAO/R model rats. Conclusion: AX alleviates LPS-induced microglial injury and has a protective effect on rat cerebral I/R injury by regulating the PPAR-γ/NF-κB pathway.展开更多
文摘Background: Emerging evidence suggests that chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect of chemotherapeutic drugs. Many experiments have proved that sodium aescinate (SA) has definite pharmacological effects such as anti-infection, anti-exudation, anti-edema, anti-tumor as well as neuroprotection, and the drug side effects are mild. However, no study has explored whether SA is involved in the analgesic effect of paclitaxel (PAC) induced neuropathic pain in rats. Methods: Rats were given an intraperitoneal injection of PAC (2.5 mg/Kg intraperitoneally on days 1, 3, 5, and 7), while SA 25 mg/kg intraperitoneally was administered daily for 14 consecutive days. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) of rats were examined on experimental days 3, 5, 7, 11, 14. All rats were sacrificed on day 15 of the experiment, and L4-6 spinal cords were removed. Subsequently, immunohistochemistry, HE staining, ELISA, RT-qPCR, Western blotting were applied to evaluate cytoskeletal protein expression (NF-L and NF-M), spinal nerve structural integrity, proinflammatory factor contents (TNF-α, IL-1β, and IL-6), and protein content of the TLR4/NF-κB pathway, respectively. Results: After the rats developed PAC induced pain behaviors, multiple injections of SA rendered the rats with elevated MWT and TWL values, decreased expression of NF-L and NF-M in the spinal cord, materially downregulated content of proinflammatory factors, and reduced amounts of TLR4 and p-NF-κB protein levels. Conclusions: The results of the present study preliminarily indicate that SA has an analgesic effect on rats with CIPN induced by PAC injection, and the mechanism may be related to blocking the TLR4/NF-κB signaling pathway, inhibiting the expression of proinflammatory factors, and alleviating cytoskeletal disorders.
文摘Objective: When nerve injury or inflammatory injury, different miRNA-mediated signal pathways are activated or inactivated, causing pain or hyperalgesia. Therefore, miRNA has become a new direction of pain mechanism research. We aimed to investigate the effect and mechanism of miR-362-3p on neuropathic pain in rats with chronic sciatic nerve injury (CCI). Methods: Neuropathic pain CCI rat model was established. Real-time-quantitative polymerase chain reaction (RT-PCR), Western blot, immunofluorescence, intrathecal injection, Enzyme-linked immunosorbent assay (ELISA), and dual luciferase reporter gene assays were used to explore the role of miR-362-3p in neuropathic pain development and the relationship between miR-362-3p and JMJD1A (Jumonji domain-containing 1A). Results: In the CCI group, the miR-362-3p level was increased and JMJD1A level was reduced in spinal cords and isolated microglia. The paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) values were increased, the secretion of inflammatory factors was reduced, and the microglial marker Iba1 expression was decreased after intrathecal administration of miR-362-3p. miR-362-3p was observed to target JMJD1A. JMJD1A elevation abolished the inhibitory effects of miR-362-3p on neuropathic pain development. Conclusion: Intrathecal administration of miR-362-3p significantly relieved neuropathic pain in CCI rats and inhibited neuroinflammation possibly through regulating JMJD1A.
文摘Purpose: This research evaluates the efficacy of astaxanthin (AX) on cerebral ischemia/reperfusion (I/R) injury in rats and elucidates the potential mechanism of its neuronal protective effect. Methods: Rats were subjected to a middle cerebral artery occlusion/reperfusion (MCAO/R) model. Fifty grown male Sprague-Dawley (SD) rats were divided into 5 groups, including sham operation group (Sham), MCAO/R group, MCAO/R+AX group, MCAO/R+ AX+ Scramble group and MCAO/R+AX+ si-PPAR-γ group. The neurological score and cerebral infarction volume were evaluated after surgery. Rat microglia (RM) were stimulated by lipopolysaccharide (LPS) to form an inflammatory environment. LPS-induced RM cells were incubated with different concentrations of AX (1, 5 or 10 μg/mL), then cell viability, the expression of microglial activation markers, including cytokines (IL-1β, IL-6 and TNF-α), cluster of differentiation 68 (CD68), inducible nitric oxide synthase (iNOS) and CD206 and the expression of PPAR-γ and phosphorylated P65 (p-P65) proteins were determined. Cells were treated with pcDNA-PPAR-γ, as well as treatment with si-PPAR-γ or PPAR-γ antagonist GW9662 before AX treatment, and then cell activation mediators were tested. Results: AX inhibits LPS-induced RM cells activation and enhanced the expression level of PPAR-γ protein in way of dose-dependent, and pcDNA-PPAR-γ treatment had the same effect as AX. While si-PPAR-γ transfection or PPAR-γ suppressant GW9662 treatment reversed the effect of AX, and cut down the level of PPAR-γ protein and augmented the level of p-P65 protein. In addition, AX treatment alleviated the infarct volume, and sensorimotor and cognitive functions of MCAO/R model rats. Conclusion: AX alleviates LPS-induced microglial injury and has a protective effect on rat cerebral I/R injury by regulating the PPAR-γ/NF-κB pathway.
