| Background and Objective:Post-operative cognitive dysfunction (POCD) is a common complication of central nervous system following anesthesia and surgery in elderly populations. It mainly refers to deficits of cognitive functions including learning and memory, and may persist for weeks, months, or even may be a permanent presence. However, the precise pathogenic mechanisms remain unknown. Studies have found surgical procedures and/or surgical trauma may trigger a postoperatice cognitive decline that is associated with a neuroinflammatory response in the hippocampus, and treat inflammatory response can attenuate POCD.Hydrogen sulfide (H2S), recently hypothesized as the third "gasotransmitter" alongside nitric oxide and carbon monoxide, has attracted extensive attention because of its multiple physiological and pathophysiological roles in various body systems. In the central nervous system, it is reported that H2S protects neurons against oxidative stress injury, attenuates lipopolysaccharide (LPS) intracerebroventricular injection induced cognitive impairment, neuronal ultrastructure damage and neuroinflammatory response. And physiological concentrations of H2S specifically potentiate the activity of the N-methyl-D-aspartate receptor and enhance the induction of hippocampus long-term potentiation, which is associated with learning and memory.In present study, cognitive function was evaluated by Morris water maze; peripheral blood tumor necrosis factor (TNF)-a, interleukin (IL)-1β、and interleukin (IL)-6were measured by enzyme-linked immunosorbent assay (ELISA); the expressions of TNF-α, IL-1β, and IL-6protein in hippocampus were determined by Western blot. Therefore the present study was designed to investigate whether sodium hydrosulfide (NaHS), a H2S donor, prevents surgical trauma-induced cognitive impairment in hepatectomy mice; and what are the possible mechanisms?Methods:One hundred and twenty Kunming male mice were randomly assigned to five groups:l)Control group (group NS; n=24).2) Sodium hydrosulfide group (group NaHS; n=24).3) Sham surgery group(group Sham; n=24).4) Surgery group (group Surgery; n=24).5) Sodium hydrosulfide plus Surgery group (group NaHS+Surgery; n=24). Cognitive function was evaluated by Morris water maze. The procedure included two steps. The first step was the place navigation test for five consecutive days. The second step was the spatial probe test on post-operative1,3,7. Mice in group NS, Sham and Surgery were given normal saline by intraperitoneal injection (i.p.) daily for3days before surgery, on surgery day, and3days after surgery, and mice in group NaHS and NaHS+surgery were administered with NaHS resolution by i.p. at the dose of5mg/kg,3days before surgery, on surgery day, and3days after surgery. On the day of surgery, mice were anesthetized i.p. with fentanyl0.2mg/kg and droperidol5mg/kg. Once anesthetized, the group Sham mice underwent laparotomy in the middle upper abdominal quadrant. The surgical wound was closed with sutures5minutes later. The group Surgery and NaHS+surgery mice were treated as in the group Sham, except that they underwent a about one-third partial hepatectomy under under general anesthesia. After accomplishment of the Morris water maze test, mice were anesthetized and blood sample (about0.8-1.2ml) were obtained via Orbital venous plexus. Samples were placed at room temperature for2hours and centrifuged(3000r.p.m.) at4℃for15min. Serum was then decanted into storage tubes and stored at-20℃until assay. TNF-a, IL-1β, and IL-6were measured by ELISA. The mice after the blood samples collected were euthanized, and hippocampus were removed and rapidly frozen at-80℃. The expressions of TNF-a, IL-1(3, and IL-6protein in hippocampus were determined by Western blot.Results:1. Morris water maze test:1) peri-operative place navigation test, all five group mice underwent water maze training for five consecutive training days. Animals in all groups were able to rescue themselves and the escape latency and swimming distance gradually decreased over the five consecutive training days. In the same time, there was no significantly differences among five groups (p>0.05).2) post-operative spatial probe test:During the probe trial, the swimming speed was not significantly different among five groups on the postsurgical1,3,7day (p>0.05). The percent time spent in target quadrant with the previously located hidden platform and the number of platform-site crossovers were not significantly different in group NaHS when compared with group NS on1,3,7day after surgery, respectively (p<0.05). The percent time spent in target quadrant with the previously located hidden platform and the number of platform-site crossovers were significantly different in group Sham when compared with group NS on1day after surgery, and there were not significantly different on3,7day after surgery, respectively (p>0.05). The percent time spent in target quadrant with the previously located hidden platform and the number of platform-site crossovers were significantly different in group Surgery when compared with group NS on1,3,7day after surgery, respectively (p<0.05). The percent time spent in target quadrant with the previously located hidden platform and the number of platform-site crossovers were significantly different in group NaHS+surgery when compared with group NS on1day after surgery (p<0.05), and there were not significantly different on3,7day after surgery, respectively (p>0.05). The percent time spent in target quadrant with the previously located hidden platform and the number of platform-site crossovers were significantly different in group Sham and group NaHS+surgery when compared with group Surgery on1,3,7day after surgery, respectively (p<0.05).2. Peripheral blood TNF-a, IL-1p and IL-6levels were measured by ELISA: Serum levels of TNF-a, IL-1β and IL-6were not significantly different in group NaHS when compared with group NS on1,3,7day after surgery, respectively (p<0.05). Compared with group NS, Serum TNF-a was increased significantly in group Sham, group Surgery and group NaHS+surgery on1day after surgery, respectively (p>0.05). and not significant different on3and7day after surgery. Serum IL-1(3and IL-6were significantly different in group Sham on1day after surgery (p<0.05), and not significant different on3and7day after surgery. Serum IL-1β and IL-6were significantly different in group Surgery on1,3day after surgery, and not significant different on7day. Serum IL-1β and IL-6were significantly different in group NaHS+surgery on1day after surgery (p<0.05), and not significant different on3and7day after surgery. Compared with group Surgery, Serum IL-1β and IL-6were significantly different in group Sham and group NaHS+surgery on1,3day after surgery (p<0.05), and not significant different on7day (p>0.05).3. Hippocampus TNF-a, IL-1β and IL-6were measured by Western blot: Hippocampus TNF-a, IL-1β and IL-6were not significantly different in group NaHS, group Sham, and group NaHS+surgery when compared with group NS on1,3,7day after surgery, respectively (p<0.05). Hippocampus TNF-a was increasrd significantly in group Surgery on1day after surgery (p<0.05), and not significant different on7day (p>0.05). IL-1β and IL-6were significantly different in group Surgery on1,3day after surgery (p<0.05), and not significant different on7day after surgery when compared with group NS. Compared with group Surgery, Hippocampus IL-1β and IL-6were significantly different in group Sham and group NaHS+surgery on1,3day after surgery (p<0.05), and not significant different on7day (p>0.05).Conclusion:1. Surgical trauma induced postoperative learning and memory function impairment in adult mice. Surgical trauma triggers peripheral systemic inflammatory response and neuroinflammatory response may played a significant role in postoperative learning and memory function deficits.2. Pre-and after surgery treatment with NaHS (5mg/kg) significantly attenuated surgical trauma induced learning and memory function deficits. The mechanism related to exogenous added the NaHS be able to reduce the expression of inflammatory cytokines. |
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