ABSTRACT
Objectives: To investigate the effect of purmorphamine (PUR), a Shh co-receptor Smoothened (Smo) agonist, on postoperative cognitive dysfunction (POCD) rat models.
Methods: Eighteen-month-old male Sprague–Dawley rats were subjected to intramedullary fixation of a tibial fracture with 7% chloral hydrate anesthesia to mimic human clinical surgery. PUR was administered via an intraperitoneal injection at a dose of 15mg/kg/day for 3 consecutive days at 6 h after surgery. The aged rats were sacrificed after performing a Morris water maze test 1, 3, and 7 days postoperatively to evaluate the expression of related proteins at the appointed time.
Results: Compared to the POCD + vehicle group and sham + PUR group, the POCD + PUR group restored neurological deficit (P = 0.01). PUR administration induced upregulation of Shh expression on postoperative day 1 (P = 0.02), which continued on the third day (P = 0.008) but dropped by the 7th day (P = 0.03). Immunofluorescent analysis, similar to western blot analysis, showed a significant increase in the autophagy-marker LC3 (P = 0.006) as well as p62 degradation (P = 0.000) in the dentate gyrus of the aged rats (P = 0.000) after PUR treatment. Importantly, LC3 was mainly found in the presynaptic and postsynaptic membranes of the hippocampus.
Conclusions: These results indicate a link between Shh and autophagy in the rat model of POCD, providing new insights into Shh signaling pathway-mediated mechanisms of neuroprotection and cognitive repair after POCD. It also provides a potential entry point for the development of clinical drugs.
KEYWORDS:
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Pei-Jun Li
Pei-Jun Li is an anesthesiologist with the Master’s degree, who has engaged in basic experimental research for four years and published many papers in Chinese domestic journals. He is expert in neurological research.
Ying-Qiang Guo
Ying-Qiang Guo is an anesthesiologist with the Master’s degree who has worked in clinical practice for 20 years and published research in the Chinese medical journal.
Pei-Yan Ding
Pei-Yan Ding is an anesthesiologist with the Master’s degree. She has worked in clinical practice for 30 years and finished several publications about anesthesiology in Chinese journals.
Ruo-Bing Liu
Ruo-Bing Liu is an anesthesiologist with the Bachelor’s degree who has works in clinical practice for 32 years. He is very responsible and has a wealth of experience at work.
Fei Deng
Fei Deng is an anesthesiologist with the Master’s degree. She specializes in ultrasound-guided nerve block anesthesia.
Xiao-Xue Feng
Xiao-Xue Feng is an anesthesiologist with the Master’s degree. She published a paper in Chinese journal. Importantly, she is very rigorous treating her works.
Wen-Jun Yan
Wen-Jun Yan is an anesthesiologist with the Doctor’s degree who has several publication in the Journal of anesthesiology and brain research. She is a masters instructor in Ningxia Medical University and is also the director of quality control Center of Anesthesiology in Gansu province which has made great contributions to the development of anesthesiology in China.