Roles Of GIK On Spleen In A Mouse Model Of Endotoxemia

Objective: To rely on LPS injection intraperitoneally to build a spleen-injured model which came from BALB/c endotoxemia mice, and to apply intervention treatment by polarized solution(Glucose-insulin-potassium) by caudal vein,and to discuss whether high concentration polarized solution had a protection effect on the spleen injury which was resulted from the endotoxemia caused by LPS.Methods: 45 BALB/c mice were divided into 3 groups by means of random number table only.The normal control group(Sham group,n=15): physiological saline was injected from abdominal cavity and caudal vein.lipopolysaccharide group(LPS group): injected 5mg/kg/d LPSintraperitoneally per day,and 3 days in total. For the first time after intraperitoneal injection of lipopolysaccharide by tail intravenous saline 10 ml/kg, followed by time pushed back, injected once every 8 hours.Polarized solution treatment group(G-I-K group):the method of LPS injection was the same as the LPS-injection group. After the first injection, 10ml/kg polarized solution(glucose:200g/L, insulin: 60IU/L, potassium: 60mmol/L,GIK)was injected from the caudal vein every 8 hours,and 3 days in total.Though observing the general situation of every group,and to measure theinterleukin-10(IL-10), tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β),in the serum and spleen tissue. By gaging the spleen index and histopathology to make clear whether polarized solution had a protective effect on spleen in mice endotoxemia.Result:1:General situation changs: Compared with the normal control group. The LPS-injection group mice showed horripilation,eyes closed skin dim,shake,activity decrease,drowsiness, eating less,polypnea,diarrhoea and weight loss after injected LPS, The symptoms was significantly lighter in GIK group.2.Comparisons of cytokine IL-10, TNF-α,IL-1β in serum:Compared the LPS-injection group with the normal control group,The expression of TNF-α and IL-1βof the LPS group mice upregulated notabally(P<0.01).Compared the GIK group with the LPS group,the expression of pro-inflammatory cytokines appeared to downregulate in the GIK group mice(P<0.05),and the of IL-10 anti-inflammatory expressed more(P<0.01).3.Comparisons of cytokine IL-10,TNF-α,IL-1β in spleen tissue: Compared the LPS-injection group with the normal control group,the expression of TNF-α and IL-1βin spleen tissue of the LPS group mice upregulated(P<0.01).Compared with the LPS group,the expression of pro-inflammatory cytokines downregulatedin the GIK group mice(P<0.01),and the of IL-10 anti-inflammatory expressed more(P<0.01).4.Splenic index:Compared with the normal control group,the spleenicindex of LPS group reduced obviously(P<0.05).Compared to the LPSgroup,the index of GIK group increased distinctly(P<0.05).5.Spleen pathological change: in the normal control group,the spleencells were intact,and the tissue structures were clear,also had no degeneration or necrosis.While,the spleen of LPS group mice was damaged obviously,and the splenic cord became broad,the tissue structure changed,spleen hyperemia,and the fragment of nucleus could be found in the white pulp.However,the damage of spleen reduced in the GIK group.No spleen hyperemia could be found.There were some sporadic white pulp in the parenchyma of spleen.The boundary between white pulp and red pulp was clear.Conclusion:1.Injection of LPS(5mg/kg) intraperitoneally could build the spleen injury model of endotoxemia mice.2.Intraperitoneal injection of LPS induced spleen injury, also it can make the mice spleen change morphologically. Compared with normal control group, LPS group were significantly damaged.Spleen congestion could be found under light microscopy and the fragment of nucleus could be found in the white pulp.The expression of pro-inflammatory factors upregulated, and the spleen index drop.3.GIK has a protective effect on the spleen injury of BALB/c mice induced by LPS. Compared with the LPS group,the spleen injury of GIK group mice significantly reduced.The expression of pro-inflammatory cytokines downregulated,relatively the anti-inflammatory expressed more,and the spleen index raised.4.Injection of LPS intraperitoneally could inducesystemic inflammatory response,upregulated the expression of pro-inflammatory factors such as TNF-α 、 IL-1β in serum.GIK could downregulated the expression of pro-inflammatory factors TNF-α、IL-1β,upregulated the anti-inflammatory factor IL-10.It indicated that GIK has a definite protective effect on the immune system of mice.