| Part ? The anesthetic effects of continuous propofol with vitamin C injected intraperitoneally on miceObjective To explore the anesthetic effects of continuous propofol or propofol combined with vitamin C injected intraperitoneally on mice.Methods Fourty mices were divided into the following 4 groups:P80 group (propofol 80mg/kg i.p.), P70+Vc50 group (propofol 70mg/kg combined with vitamin C 50mg/kg i.p.), P55+Vc100 group (propofol 55mg/kg combined with vitamin C 100mg/kg i.p.) and P50+Vc200 group (propofol 50mg/kg combined with vitamin C 200mg/kg i.p.) (n=10). Propofol/vitamin was injected intraperitoneally at the same time every day for 6 days. The induction time and duration time were observed and recorded.Results1. Compared with that of the P80group, the duration time of P55+VC100 group and P50+VC200 group was shorter at the first, second and third day (P<0.05)2. In all the experimental groups, the duration time of the other five day was shorter than that of the first day (P<0.01); In P50+VC200 group, the duration time of the other four day was shorter than that of the second day, (P<0.01)3. The rate of the loss of righting reflex (LORR) in each group was decreased gradually from the first day to the sixth dayDiscussions:Vitamin C reduced the inductive dose and the maintainance dose of propofol. Combined use of vitamin C increased the duration time of repeated intraperitoneal injection of propofol. Moreover, combined use of vitamin C reduced the dose-related side effects of propofol.Part II Effects of vitamin C on the propofol anesthesia and antioxidant activity in miceObjective To explore the effects of combined use of vitamin C with propofol on the anesthetic effect of propofol and on the antioxidant activity in C57BL/6 mice.Methods 150 mice were randomly divided into the following two groups:The part of equivalent threshold dose of propofol combined with vitamin C group and the propofol (propofol 80mg/kg i.p.) combined with different dose of vitamine C group. And each of them included some subgroups:The part of equivalent threshold dose of propofol combined with vitamin C including 5 groups:NS group (saline of same volume i.p.), PPF80 group (propofol 80mg/kg i.p.), PPF70+VC50 group (propofol 70mg/kg combined with vitamin C 50mg/kg i.p.), PPF55+VC100 group (propofol 55mg/kg combined with vitamin C 100mg/kg i.p.), PPF50+VC200 group (propofol 50mg/kg combined with vitamin C 200mg/kg i.p.). The part of propofol with different doses of Vc including 5 groups:NS group (saline of same volume i.p.), PPF80 group (propofol 80mg/kg i.p.), PPF80+Vc50 group(propofol 80mg/kg combined with vitamin C 50mg/kg i.p.), PPF80+Vc100 group (propofol 80mg/kg combined with vitamin C 100mg/kg i.p.), PPF80+Vc200 group (propofol 80mg/kg combined with vitamin C 200mg/kg i.p.). The propofol and vitamin C were injected intraperitoneally once a day.The induction time of vitamin C with propofol by injection on C57BL/6 mice were recorded, and the MDA, SOD, LDH in serum, brain and lung tissue were measured, and the expression of NF-?B, Nrf2 in brain were detected through immunohistochemistry analysis.Results1. In the subgroups of equivalent threshold dose of propofol combined with vitamin C group, the induction time was no significant difference (P>0.05); in the subgroups of the propofol 80mg/kg combined with different doses of Vc group, the induction time has no significant difference (P>0.05);2.In the part of equivalent threshold dose of propofol combined with vitamin C, compared with NS group, the level of LDH of serum in P80 group was increased (P<0.05), compared with PPF80 group, the level of LDH of serum in PPF70+Vc50 group was decreased (P<0.01);3.In the part of equivalent threshold dose of propofol combined with vitamin C group, compared with that of PPF80 group, the activities of SOD of brain tissue in PPF55+Vc100 group and PPF50+Vc200 group were increased (P<0.05);4.In the part of equivalent threshold dose of propofol combined with vitamin C group, compared with that of PPF80 group, the level of MDA of lung tissue in PPF50+Vc200 group was decrease (P<0.05), the levels of LDH of serum PPF70+Vc50 group and PPF55+Vc100 group were decreased (P<0.05);5.In the propofol 80mg/kg with different doses of Vc group, compared with that of NS group, the level of MDA of serum in PPF80+Vc200 group was decreased (P<0.05), compared with that of PPF80 group, the level of MDA of serum in PPF80+Vc200 group was decreased (P<0.01); compared with that of PPF80+VC50 group, the level of MDA of serum in PPF80+Vc200 group was decreased (P<0.05), compared with that of the NS group, the level of LDH of serum in PPF80 group was increased (P<0.05), compared with that of PPF80 group, the level of LDH of serum in PPF80+Vc100 group was decreased (P<0.05);6.In the part of propofol 80mg/kg with different doses of Vc group, compared with that of NS group, the activity of SOD of brain tissue in PPF80+Vc100 group was increased (P<0.05); compared with that of PPF80 group, the activity of SOD of brain tissue in PPF80+Vc100 group was increased (P<0.01);7.In the propofol 80mg/kg with different doses of Vc group, compared with that of the NS group, the activity of SOD of lung tissue in PPF80+Vc200 group was increased (P<0.01), compared with that of the PPF80 group, the activity of SOD of lung tissue in PPF80+Vc200 group was increased (P<0.05), compared with that of PPF80 group, the levels of LDH of lung tissue in PPF80+Vc50 group, PPF80+Vc100 group and PPF80+Vc200 group were decreased (P<0.05).8.In the part of equivalent threshold dose of propofol combined with vitamin C group, the expression of NF-?B in brain sections in the other groups were than that of the NS group (P<0.01); compared with that of PPF80 group, the expression of NF-?B of brain tissue sections in the groups with vitamin C were lower (P<0.01); compared with that of PPF70+VC50 group, the expression of NF-?B of brain tissue sections in PPF55+VC100 group and PPF50+VC200 were decreased (P<0.01); compared with that of PP55+VC100 group, the expression of NF-?B of brain sections in PPF50+VC200 group was decreased (P<0.01).9.In the part of equivalent threshold dose of propofol combined with vitamin C group, the expression of Nrf2 of brain tissue sections in the remaining group were increased (P<0.01); the expression of Nrf2 of brain tissue sections in the PPF70+VC50 group was more than that of the PPF80 group (P<0.05); the expression of Nrf2 of brain tissue sections in PPF55+VC100 group and PPF50+VC200 group were increased (P<0.01); compared with that of PPF80+VC50 group, the expression of Nrf2 of brain tissue sections in PPF50+VC200 group was increased (P<0.01); compared with PP80+VC100 group, the expression of Nrf2 of brain tissue sections in PPF50+VC200 group was increased (P<0.01).10. In the part of propofol 80mg/kg with different doses of Vc, compared with the expression of NF-?B in brain tissue sections in the other groups were higher than that in NS group (P<0.01); compared with PPF80 group,the expression of NF-?B in brain tissue sections in the groups with vitamin C were decreased (P<0.01); compared with PPF80+VC50 group, the expression of NF-?B of brain tissue sections in PPF50+VC200 group were decreased (P<0.01); compared with PP80+VC100 group, the expression of NF-kB of brain tissue sections in PPF80+VC200 group was lower (P<0.01).11.In the part of propofol 80mg/kg with different doses of Vc,compared with the NS group, the expression of Nrf2 of brain tissue sections in the remaining group were increased (P<0.01); compared with PPF80 group, the expression of Nrf2 of brain tissue sections in the PPF80+VC50 group was higher (P<0.05), the expression of Nrf2 of brain tissue sections in PPF80+VC100 group and PPF80+VC200 group were increased (P<0.01); compared with PPF80+VC50 group, the expression of Nrf2 of brain tissue sections in PPF80+VC200 group was higher (P<0.01); compared with that of PP80+VC100 group, the expression of Nrf2 in brain tissue sections in PPF80+VC200 group was increased (P<0.01).Discussions Combined use of Vitamin C reduced the inductive time and the maintainance time of propofol, but there was no dose-dependent effect. The SOD activity of brain and lung tissue under the propofol anesthesia was increased by combined use of vitamin C, and the MDA, LDH levels in serum and lung tissue was decreased, which reduced the lipid peroxidation injury and might play a role in cell protection. Vitamin C can inhibit NF-?B activity and promote Nrf2 expression.Conclusion Vitamin C reduced the inductive dose and the maintainance dose of propofol. Combined use of vitamin C increased the duration time of repeated intraperitoneal injection of propofol, enhanced the radical scavenging ability of mice and inhibit the lipid peroxidation. In addition, Vitamin C can inhibit NF-?B activity and promote Nrf2 expression. |
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