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Protective Effect of RNase on Unilateral Nephrectomy-Induced Postoperative Cognitive Dysfunction in Aged Mice.

Chen C, Cai J, Zhang S, Gan L, Dong Y, Zhu T, Ma G, Li T, Zhang X, Li Q, Cheng X, Wu C, Yang J, Zuo Y, Liu J - PLoS ONE (2015)

Bottom Line: We found that perioperative administration of RNase: 1) attenuated unilateral nephrectomy-induced cognitive impairment at day 3 after surgery; 2) reduced the hippocampal cytokines mRNA production and serum cytokines protein production at day 1 and day 7 (for MCP-1) after surgery, and; 3) inhibited hippocampal apoptosis as indicated by cleaved caspase-3 western blot and TUNEL staining at day 1 after surgery.In addition, a trend decrease of total serum RNA levels was detected in the RNase treated group after surgery compared with the untreated group.Further, our protocol of RNase administration had no impact on the arterial blood gas analysis right after surgery, kidney function and mortality rate at the observed days postoperatively.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

ABSTRACT
Postoperative cognitive dysfunction (POCD) is a common complication after surgery, especially for elderly patients. Administration of RNase has been reported to exhibit neuroprotective effects in acute stroke. However, the potential role of RNase on POCD is unknown. Therefore, we sought to investigate whether RNase treatment could mitigate unilateral nephrectomy induced-cognitive deficit in aged mice. In the present study, twelve-month-old mice were administered RNase or an equal amount of normal saline perioperatively. All mice underwent Morris Water Maze (MWM) training 3 times per day for 7 days to acclimatize them to the water maze before surgical operation, and testing on days 1, 3 and 7 after surgery. We found that perioperative administration of RNase: 1) attenuated unilateral nephrectomy-induced cognitive impairment at day 3 after surgery; 2) reduced the hippocampal cytokines mRNA production and serum cytokines protein production at day 1 and day 7 (for MCP-1) after surgery, and; 3) inhibited hippocampal apoptosis as indicated by cleaved caspase-3 western blot and TUNEL staining at day 1 after surgery. In addition, a trend decrease of total serum RNA levels was detected in the RNase treated group after surgery compared with the untreated group. Further, our protocol of RNase administration had no impact on the arterial blood gas analysis right after surgery, kidney function and mortality rate at the observed days postoperatively. In conclusion, perioperative RNase treatment attenuated unilateral nephrectomy-induced cognitive impairment in aged mice.

No MeSH data available.


Related in: MedlinePlus

Effect of RNase administration on total serum RNA after unilateral nephrectomy in aged mice.The concentration of total serum RNA at day 1, day 3 and day 7 after surgery in aged mice from all three groups and the naïve control group were measured. Data are presented as mean ± SEM (n = 5 per group; n = 6 for naïve control group). *P<0.05 vs. S-S group. S-S, sham surgery plus placebo; S-P, surgery plus placebo; S-R, surgery plus RNase.
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pone.0134307.g003: Effect of RNase administration on total serum RNA after unilateral nephrectomy in aged mice.The concentration of total serum RNA at day 1, day 3 and day 7 after surgery in aged mice from all three groups and the naïve control group were measured. Data are presented as mean ± SEM (n = 5 per group; n = 6 for naïve control group). *P<0.05 vs. S-S group. S-S, sham surgery plus placebo; S-P, surgery plus placebo; S-R, surgery plus RNase.

Mentions: As one of the important DAMPs, exRNA, such as ribosomal RNA, transfer RNA, and messenger RNA, may be released from damaged cells during surgical injury. Therefore, we measured the total serum RNA levels at day 1, day 3 and day 7 after surgery in the S-S, S-P, and S-R group, in order to evaluate the functional role of exRNA in nephrectomy induced cognitive dysfunction. We have found total serum RNA was significantly increased in the S-P group compared with that of the S-S group at day 1 (3.40± 0.49 v.s. 2.41 ± 0.08, *P<0.05, n = 5) and day 3 (3.00 ± 0.16 v.s. 2.38 ± 0.09, *P<0.05, n = 5) after surgery, whereas there was no difference between S-S group and Naïve group (n = 6 for naïve group) (Fig 3). Notably, total serum RNA level had a decreasing trend in the S-R group at day 3 (P = 0.15) and day 7 (P = 0.09) postoperatively (n = 5) (Fig 3). This suggests that perioperative administration of RNase, the counterpart of exRNA, may reduce the serum levels of RNA. Taken together, these data suggest that the protective effect of RNase treatment on the unilateral nephrectomy-induced cognitive dysfunction might be associated with the reduction of exRNA released after surgical injury.


Protective Effect of RNase on Unilateral Nephrectomy-Induced Postoperative Cognitive Dysfunction in Aged Mice.

Chen C, Cai J, Zhang S, Gan L, Dong Y, Zhu T, Ma G, Li T, Zhang X, Li Q, Cheng X, Wu C, Yang J, Zuo Y, Liu J - PLoS ONE (2015)

Effect of RNase administration on total serum RNA after unilateral nephrectomy in aged mice.The concentration of total serum RNA at day 1, day 3 and day 7 after surgery in aged mice from all three groups and the naïve control group were measured. Data are presented as mean ± SEM (n = 5 per group; n = 6 for naïve control group). *P<0.05 vs. S-S group. S-S, sham surgery plus placebo; S-P, surgery plus placebo; S-R, surgery plus RNase.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4520469&req=5

pone.0134307.g003: Effect of RNase administration on total serum RNA after unilateral nephrectomy in aged mice.The concentration of total serum RNA at day 1, day 3 and day 7 after surgery in aged mice from all three groups and the naïve control group were measured. Data are presented as mean ± SEM (n = 5 per group; n = 6 for naïve control group). *P<0.05 vs. S-S group. S-S, sham surgery plus placebo; S-P, surgery plus placebo; S-R, surgery plus RNase.
Mentions: As one of the important DAMPs, exRNA, such as ribosomal RNA, transfer RNA, and messenger RNA, may be released from damaged cells during surgical injury. Therefore, we measured the total serum RNA levels at day 1, day 3 and day 7 after surgery in the S-S, S-P, and S-R group, in order to evaluate the functional role of exRNA in nephrectomy induced cognitive dysfunction. We have found total serum RNA was significantly increased in the S-P group compared with that of the S-S group at day 1 (3.40± 0.49 v.s. 2.41 ± 0.08, *P<0.05, n = 5) and day 3 (3.00 ± 0.16 v.s. 2.38 ± 0.09, *P<0.05, n = 5) after surgery, whereas there was no difference between S-S group and Naïve group (n = 6 for naïve group) (Fig 3). Notably, total serum RNA level had a decreasing trend in the S-R group at day 3 (P = 0.15) and day 7 (P = 0.09) postoperatively (n = 5) (Fig 3). This suggests that perioperative administration of RNase, the counterpart of exRNA, may reduce the serum levels of RNA. Taken together, these data suggest that the protective effect of RNase treatment on the unilateral nephrectomy-induced cognitive dysfunction might be associated with the reduction of exRNA released after surgical injury.

Bottom Line: We found that perioperative administration of RNase: 1) attenuated unilateral nephrectomy-induced cognitive impairment at day 3 after surgery; 2) reduced the hippocampal cytokines mRNA production and serum cytokines protein production at day 1 and day 7 (for MCP-1) after surgery, and; 3) inhibited hippocampal apoptosis as indicated by cleaved caspase-3 western blot and TUNEL staining at day 1 after surgery.In addition, a trend decrease of total serum RNA levels was detected in the RNase treated group after surgery compared with the untreated group.Further, our protocol of RNase administration had no impact on the arterial blood gas analysis right after surgery, kidney function and mortality rate at the observed days postoperatively.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

ABSTRACT
Postoperative cognitive dysfunction (POCD) is a common complication after surgery, especially for elderly patients. Administration of RNase has been reported to exhibit neuroprotective effects in acute stroke. However, the potential role of RNase on POCD is unknown. Therefore, we sought to investigate whether RNase treatment could mitigate unilateral nephrectomy induced-cognitive deficit in aged mice. In the present study, twelve-month-old mice were administered RNase or an equal amount of normal saline perioperatively. All mice underwent Morris Water Maze (MWM) training 3 times per day for 7 days to acclimatize them to the water maze before surgical operation, and testing on days 1, 3 and 7 after surgery. We found that perioperative administration of RNase: 1) attenuated unilateral nephrectomy-induced cognitive impairment at day 3 after surgery; 2) reduced the hippocampal cytokines mRNA production and serum cytokines protein production at day 1 and day 7 (for MCP-1) after surgery, and; 3) inhibited hippocampal apoptosis as indicated by cleaved caspase-3 western blot and TUNEL staining at day 1 after surgery. In addition, a trend decrease of total serum RNA levels was detected in the RNase treated group after surgery compared with the untreated group. Further, our protocol of RNase administration had no impact on the arterial blood gas analysis right after surgery, kidney function and mortality rate at the observed days postoperatively. In conclusion, perioperative RNase treatment attenuated unilateral nephrectomy-induced cognitive impairment in aged mice.

No MeSH data available.


Related in: MedlinePlus