| 刘康，周芳，赵博，黄亚医，王雅枫.胃饥饿素在糖尿病神经病理性疼痛中的作用及对大鼠脊髓P2X4/NLRP3表达的影响[J].神经损伤功能重建,2019,14(8):379-382 |
| 胃饥饿素在糖尿病神经病理性疼痛中的作用及对大鼠脊髓P2X4/NLRP3表达的影响 |
| Role of Ghrelin on Diabetic Neuropathic Pain and Its Effect on P2X4/NLRP3 Expression inSpinal Cord of Rats |
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| DOI： |
| 中文关键词: 胃饥饿素 糖尿病神经病理性疼痛 嘌呤受体2X-4 NOD样受体-3 |
| 英文关键词: ghrelin diabetic neuropathic pain P2X4 NLRP3 |
| 基金项目:湖北省自然科学基金（No.2017CFB267）
中央高校基本科研业务费专项基金
（No.2042018kf0161 |
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| 中文摘要: |
| 目的：探讨胃饥饿素（Ghrelin）在糖尿病神经病理性疼痛中的作用及对大鼠脊髓嘌呤受体2X-4/NOD
样受体-3（P2X4/NLRP3）表达的影响。方法：健康成年雄性SD大鼠40只，随机分为5组，每组8只：正常+
Ghrelin组（NG组）、正常+[D-Lys3]-GHRP-6组（ND组）、糖尿病组（D组）、糖尿病+Ghrelin组（DG组）、糖尿
病+Ghrelin+[D-Lys3]-GHRP-6 组（DGD 组）。[D-Lys3]-GHRP-6 为 Ghrelin 特异性抑制剂。NG 组腹腔注射
Ghrelin 200 μg/kg 6周，ND组腹腔注射[D-Lys3]-GHRP-6 50 mg/kg 6周。腹腔注射1%链脲佐菌素-柠檬酸盐
缓冲液 60 mg/kg制备大鼠糖尿病模型，造模成功后3 d，腹腔注射Ghrelin 200 μg/kg 6周，DGD组腹腔注射
Ghrelin 200 μg/kg+[D-Lys3]-GHRP-6 50 mg/kg 6周。分别于第2，4，6周测定大鼠机械痛阈（MWT）及坐骨神
经导速率（MNCV）；6周后处死大鼠，尼氏染色观察脊髓病理学变化，电镜观察腓肠神经病理学改变，Western blot法检测脊髓Ghrelin、P2X4、NLRP3和IL-1β表达水平。结果：与NG组比较，ND组脊髓Nissl染色和
腓肠神经电镜显示细胞结构正常，MWT和MNCV无明显变化，P2X4、NLRP3、IL-1β表达水平差异无统计学
意义（P＞0.05）；D组脊髓Nissl染色和腓肠神经电镜显示细胞部分受损，MWT、MNCV显著降低；Ghrelin表
达降低，P2X4、NLRP3、IL-1β显著升高（P＜0.05）。与D组比较，DG组中脊髓Nissl染色和腓肠神经电镜显
示细胞结构相对正常，MWT 和 MNCV 明显升高，Ghrelin 表达升高，P2X4、NLRP3、IL-1β表达降低（P＜ 0.05）。与DG组比较，DGD组中脊髓Nissl染色和腓肠神经电镜细胞结构破坏严重，MWT和MNCV明显降
低，Ghrelin表达降低，P2X4、NLRP3、IL-1β表达升高（P＜0.05）。结论：Ghrelin可能通过P2X4/NLRP3通路参
与了糖尿病神经病理性疼痛的调控。 |
| 英文摘要: |
| To evaluate the role of ghrelin on diabetic neuropathic pain and its effect on the
expression of purinergic receptor 2X-4/NOD-like receptor-3 (P2X4/NLRP3). Methods: Forty male
Sprague-Dawley rats were randomly allocated into 5 groups (n=8 each): normal + ghrelin group (group NG),
normal + [D-Lys3]-GHRP-6 group (group ND), diabetes group (group D), diabetes + ghrelin group (group DG),
and diabetes + ghrelin + [D-Lys3]-GHRP-6 group (group DGD). [D-Lys3]-GHRP-6 served as a ghrelin-specific
inhibitor. Group NG received intraperitoneal injections of 200 μg/kg ghrelin for 6 weeks, and group ND received
intraperitoneal injections of 50 mg/kg [D-Lys3]-GHRP-6 for 6 weeks. Diabetes mellitus was induced by
intraperitoneal injections of 60 mg/kg 1% streptozotocin. Three days after establishment of diabetes model,
group DG was intraperitoneally given 200 μg/kg ghrelin and group DGD given 200 μg/kg ghrelin plus 50 mg/kg
[D-Lys3]-GHRP-6 for 6 weeks. Mechanical withdrawal threshold (MWT) and motor nerve conduction velocity
(MNCV) were measured at 2, 4, and 6 weeks. After 6 weeks the rats were sacrificed. Rat spinal cords were
examined for pathology change by Nissl staining and pathology change of the sural nerve by electron microscopy
(EM). Expression of ghrelin, P2X4, NLRP3, and IL-1β in the spinal cord was detected by western blot. Results:
Compared with group NG, group ND spinal Nissl staining and sural nerve EM showed normal spinal cell
structure; there was no significant change in MWT and MNCV and no significant difference in the expression of
P2X4, NLRP3, and IL-1β (P>0.05). Spinal Nissl staining and sural nerve EM of group D showed partial cellular
damage, decreased MWT and MNCV, down-regulated expression of ghrelin, and up-regulated expression of
P2X4, NLRP3, and IL-1 β (P<0.05). Compared with group D, group DG showed normal spinal cell structure,
increased MWT and MNCV, up-regulated expression of ghrelin, and down-regulated expression of P2X4,
NLRP3, and IL-1 β (P<0.05). Compared with group DG, group DGD showed severe cell structure damage,
decreased MWT and MNCV, down-regulated expression of ghrelin, and up-regulated expression of P2X4,
NLRP3, and IL-1 β (P<0.05). Conclusion: Ghrelin may be involved in diabetic neuropathic pain through the P2X4/NLRP3 signaling pathway. |
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