| Backgrand:Ovarian cancer is one of the common malignant tumors of the female reproductive organs.WHO worldwide data statistics,in the female genital malignant tumors,the incidence of ovarian cancer is the third in gynecological malignancies,and the mortality rate is the first,which seriously threatens women's lives.Due to the deep pelvic cavity of the ovaries and the small size,ovarian cancer symptoms often do not have typical specificity in the early stage,and about 70% of patients have been found to be advanced.Cancer pain is one of the main causes of pain in patients with advanced cancer,which seriously affects the quality of life of patients and is increasingly valued by people.At present,the mechanism of pain conduction is not very clear.Some studies have found that it is related to a series of reactions caused by certain substances produced by tumors,such as prostaglandin and endothelin,which excite their receptors.In the past few years,endothelin(ET)has gradually received attention in the study of the pathogenesis of cancer pain.It is A polypeptide composed of 21 amino acids,which is widely found in vascular endothelium and various tissues and cells,including three subtypes of ET-1,ET-2 and ET-3.It exerts corresponding biological effects by binding to endothelin receptor(ETR),including endothelin A receptor(ETAR)and endothelin B receptor(ETBR).Endothelin receptor is a signal pathway of pain nerve signal transmission.Endothelin receptor can selectively stimulate inflammatory mediators related to neuropathic or carcinogenic pain,which may trigger the pain state in humans and other animals.The literature indicates that ETAR is mainly distributed on peripheral sensory neurons.ETBR was mainly expressed in the schwann cells in the dorsal root ganglion and sciatic nerve,while ETBR was also expressed in the keratinocytes secreting opioids.Dorsal root ganglion(DRG)is the hubof various information and some nociceptive stimuli of the body from the periphery to the central nervous system.The purpose of this study was to investigate the changes in the ultrastructural level of dorsal root ganglia in the ovarian cancer model with the intervention of endothelin and its receptors,in order to further reveal the mechanism of morphological development and conduction of ovarian cancer.Objective:To investigate the effects of endothelin,endothelin receptor agonists and endothelin receptor antagonists on the behavior of mice by establishing an animal model of ovarian cancer pain,and to observe the dorsal root ganglia of mice from the ultrastructural level.The above-mentioned injury conditions provide a morphological basis for the mechanism of endothelin,endothelin receptor agonists and endothelin receptor antagonists on ovarian cancer pain,thus providing new ideas for the treatment of ovarian cancer pain.Method:1.60 female healthy Kunming mice(Hebei Medical University Experimental Animal Center),aged 5 weeks,about 25 grams.According to the random number table method,it was divided into normal control group,sham operation group,model group,model ET intervention group,model BQ123 intervention group and model BQ788 intervention group,with 10 rats in each group.The ascites tumor S180 tumor cells were inoculated into the left ovary of mice by the dorsal approach,and a mouse model of orthotopic transplantation of ovarian cancer was established.The model ET intervention group,model BQ123 intervention group and model BQ788 intervention group were injected endothelin ET-1,ETA receptor antagonist BQ123 and ETB receptor antagonist BQ788 into the spinal canal on the 8th,10 th and12th day after operation,once a day.2.Application of Von-Frey fiber mechanical stimulator and BME-410 A thermal pain stimulator on the day before modeling(Day 0),Day 7 and Day 9after model establishment(Day 1 after administration),Day 11(the third day after administration)and Day 13(the fifth day after administration),themechanical reflex foot reflex threshold(MWT)and the heat-shrinking foot latency of the left and right hind paws of different groups of mice were determined.3.After administration on day 13,the mice were sacrificed,and the vertebral plates were cut vertically from the neck of the mice to expose the spinal cord completely.The peripheral ribs are a sign of the first lumbar vertebra.First lumbar dorsal root ganglion is located in the intervertebral foramen,found in the intervertebral foramen of the first lumbar dorsal root ganglia,then separate and remove each lumbar spinal ganglion,saline flushing,quickly put in fixed liquid,stored in 4 ?,preparing section,to observe different groups mouse lumbar dorsal root ganglion sensory neurons(gather)of electron microscopy.Results:Behavioral experimental data results show1.There was no difference between the normal control group and the sham operation group.The thermopathic and mechanical hyperalgesia thresholds of the model control mice were lower than those of the sham-operated mice,and the pain was significantly correlated with tumor production.2.The model intervention group was compared with the model control group:The threshold of thermal and mechanical hyperalgesia in model ET intervention group was significantly lower than that in model control group;the model BQ123 intervention group was more hot and mechanically sensitive than the model control group.The thresholds were all increased;the thermopathic and mechanical allodynia thresholds of the model BQ788 intervention group were higher than those of the model control group.Endothelin is closely related to the degree of cancer pain in ovarian cancer.3.There were differences between the three groups in the model intervention ET intervention group.Compared with the model BQ123 intervention group and BQ788 intervention group,the thermal sensitization and mechanical allodynia threshold of the model ET intervention group werelower than those of the model BQ123 intervention group.The thermal pain sensitivity and mechanical allodynia threshold of the model BQ788 intervention group were higher than those of the model BQ788 intervention group.Different endothelin receptor antagonists have different effects on ovarian cancer pain.The results of electron microscopy show1.There was no significant difference between the normal control group and the sham operation group.Lysosomes,mitochondria,endoplasmic reticulum can be seen in the cytoplasm,and a nucleolus can be seen in the nucleus.The myelin sheath is dense in the periphery.2.The model group has a destructive performance.The nuclear membrane notch can be seen,the mitochondria in the cytoplasm become dark,glial cells,tissue edema,lysosomes increase,and some mitochondria vacuoles.3.Destructive performance occurred in the ET-1 group.It can be seen that lysosomes increase,nuclear membrane notch,disappear,endoplasmic reticulum pyknosis,vacuolization,mitochondria increase,vacuolization,swelling and disappearance.4.123 groups performed lighter than the model group.The lysosomes of the dorsal root ganglion cells increased slightly,and the glial cells were pseudo-foot-like ganglion cells,and the mitochondria increased and deformed.5.The damage performance of the 5,788 group was lighter than that of the model group.Mitochondria diffuse vacuoles,sputum disappears,nuclear irregularities,lysosomes increase,myelin sheath is mildly edematous,and endoplasmic reticulum is normal.Conclusion:1.Endothelin and its receptors are involved in the transmission of ovarian cancer pain,and different endothelin receptor antagonists have different effects on cancer pain.2.Observed ovarian cancer and ET-1 on the dorsal root ganglion cells ofmice by electron microscopy.Endothelin receptor blockers can alleviate this damage. |
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