| Neuropathic pain is one kind of chronic pain, which pathogenesis is complicated. Thereis the Following creation of Neurological function disorder.It has great progress in the pastyears in research on neuropathic pain in physiology、phamacology、molecular biology. WhilePathogenesis and effective theropy is ever the hotspot in the study.Drugs in the clinic are alsokind of antidepressants and opioid receptors,which have great sideeffects and influentpacients life quality.Accordingly, searching out a new effective regulatory factor and way hasclinical significance for neuropathic pain petients and disclosing the molecule mechanism.Fructus gardeniae is a commen medicine for analgesics in traditional chinese medicine. Theeffective constituent of Fructus gardeniae is iridoid glycoside. Geniposide is the primaryeffective constituent of it. Geniposide has analgesic and sadation effect on central nervoussystem and anti-inflammatory and repair effect on injured tissue. The research investigatedthe commen craft of Geniposide, and ascertained the best craft, observing on abstractivesolvent、abstractive potency、time、rature、bace-flowing times and so on, compared withstandardized geniposide. The best craft is: Rature1:7，alcohol80%，backflowing1hour inwater85℃for2hours，geniposide getted. The UPLC method we designed is a qualifiedoptimal design with high sensitivity, short test time and high systematical application, whichdepended on the integrated survey about the content of Geniposide and The actual extractio,and the method was appropriate for Geniposide extraction. We constructed CCI model in ratin the second part of the study for further research on geniposide.The standard substance ofGeniposide received had been intragastric administrated to rats, and observed what influenceit had on the expression of TNF-α and pain threshold of CCI rats.Within21days after CCI surgery observation period, all rats were maintained in good health, there is no obvious signs of wound infection, fur is good, weight decreased slightly,overall activity is in good condition, digits are together on surgery side, foot is slightly valgus.Rats tend to take protective posture, the suffered foot often suspended in air, the center ofbody gravity toward to the contralateral limb, suggesting that after spinal nerve injurysurgery, the foot on surgical side appears spontaneous performance of pain, in thesham-operated side found no foot deformities and behavioral abnormalities. Animals aftersurgery appeared to have pathological pain behavioral changes, including spontaneous pain,allodynia, etc. The model is stable, high repeatability, low pain threshold differences withinthe group. Through the pain threshold analysis, it was concluded that to CCI model,neuropathic pain reaching a peak of mechanical allodynia on postoperative day7, reachingthe second small peak postoperative on day14, suggesting that sciatic nerve ligationsignificantly reduced pain threshold and caused hyperalgesia.The function of cytokine and initial stage inflammation immune response are generallyconsidered to be the extremely basic element in noxious stimulation and regeneration afternerve injury.TNF-a expression on spinal cord,and activates astrocyte nearby,which canactivates and hyperplasia others nerby through the net in Cell-cell mediated by TNF-a. It hadproved that Pain Threshold is lower on the7thand14thd,at the same time TNF-a expressedhigher.So acute neuropathic pain on CCI model rat maybe relative to TNF-a high expressionand astrocyte continuing hyperplasia. TNF-a participates initial phase and astrocyteparticipates continueral allodynia.The study desined miRNA-21expression on CCI rats spinalcord and astrocyte and aim to explane the mechanism by gene regulation.Anti-epileptic Gabapentin can relieve neurothic pain and astrocyte changes after CCIespecially on Postorperation7thd and continue to14thd.It conclude that Gabapentin can relievepain by the way restrain astrocyte activation.In conclusion, astrocytes involved in the maintenance of hyperalgesia, which couldremain the hyperalgesia.miRNA-21was one of miRNAs, which were found early, and widelyexisted in tissues and cells of human body. miRNA-21regulated the differentiation, proliferation and apoptosis of cells through the target genes. It had been found that miR-21was highly expressed in the tissues of lung cancer, breast cancer, glioblastoma, gastric cancer,pancreatic cancer, liver cancer, colon cancer and ovarian cancer, especially in Star gliomas.And it had been validated that miRNA-21involved in the regulation of tumor invasiveness.Some studies had confirmed that miRNA-21was involved in the upregulated gene spectrumin the proximal neuro-tissue injured by the model of neuropathic pain. It have Proved thatmiRNA-21upregulating on CCI model proximate spinal nerve tissue,we infer thatmiRNA-21maybe relative to astrocyte activation.It can make for a new target on neuropathicpain diagnosis and treatment.Is the same way and meaning of Gabapentin on astrocyte. Theexperiment collects groups of rats spinal cord and clearaged by Trizol to tissue RNA.AnalysismiRNA-21expression on spinal cord before and after interrupt by Gabapentin.It showedmiRNA-21had tendency up-regulated on1std after CCI, but had no significant statistics.While miRNA-21expression up-regulated on CCI7thd and14thd compared to controlgroup. MiRNA-21expression in Gabapentin group down-regulated compared to CCI modelgroup on ether7thd or14thd. The results showed miRNA-21have high expression on spinalcord after CCI, and gabapentin can relieve pain through down regulate its expression.The experiment hint mechanism analgetic function of Gabapentin maybe relative toregulate miRNA-21and restrain the Astrocyte cytostasis.It needs further more experiments for whether geniposide can influent Astrocytecytostasis in CCI rat soinal cord and regulate miRNA-21expression in vitro and vivo. |
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