Effect of ethyl pyruvate on cognitive function in sepsis rats

doi:10.3877/cma.j.issn.2096-1537.2018.02.015

Abstract

Abstract:

Objective

To determine the effect of ethyl pyruvate on cognitive function in rats with sepsis and its underling mechanism.

Methods

Part Ⅰ: The sepsis model was conducted by cecal ligation and puncture (CLP). Fifty healthy male SD rats were randomly divided into 5 groups (n=10): sham operation group (group C), sepsis group (group S), sepsis + High mobility group box-1 (HMGB1) treatment group (group SH), sham + HMGB1 treatment group (group H), sepsis + ethyl pyruvate treatment group (group SE). In the group SH and H, 5 μl of 0.5 μg/μl recombinant HMGB1 was injected into the lateral ventricle and 5 μl of saline was administered to the other 3 groups. In the SE group, ethyl pyruvate (80 mg/kg) was injected subcutaneously, and the remaining 4 groups were given the same volume of saline. Severn day survival curve analysis was performed among different groups. Part Ⅱ: Group dividing and experiment process are the same as before (n=20). Forty-eight hours after CLP or CLP sham a 6-days positioning navigation training of Morris water maze and the subsequent space exploration experiment was used to test cognitive ability. Part Ⅲ: Forty-eight hours post CLP or CLP sham, the brain tissue was harvest forbrain water content. Nissl′s staining was used to observe the number of neurons in the hippocampus and RT-qPCR was used to detect mRNA expression of hippocampal HMGB1, Ionized calcium bindingadaptor molecule-1 (Iba-1), Tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), and amyloid precursor protein (APP).

Results

(1) Compared to group C, the survival rate of group S and SH was significantly decreased (P<0.05) and there was no significant difference between group H and SE (P>0.05). (2) There was no difference in swimming speed among the five groups in Morris water maze experiment. Compared to group C, swimming distance and escape latency were longer and the percentage of staying time passing through virtual platform and target quadrant decreased significantly (P<0.05) in group S, SH, Hgroup SE. The swimming distance and escape latency increased in SH group and decreased in S group relative group S. (3) Compared to group C, brain water increased in the other four groups (P<0.05). In addition, brain water increased in group SH and decreased in group SE and H relative group S (all P<0.05). Nissl staining showed that compared to group C, group S, SH, H and SE showed a decreased number of normal neurons in hippocampal CA1 region (P<0.05). The number of neurons decreased in group SH and increased in group SE compared to group S (both P<0.05). Compared to group C, the expressions of HMGB1, TNF-α, IL-1β, Iba-1 and APP mRNA in group S and SH were up-regulated (P<0.05). The expression of HMGB1, TNF-α, IL-1β and Iba-1 mRNA was also up-regulated in SE group (P<0.05) but there was no difference of APP mRNA expression between group SE and C (P>0.05). Compared with S group, the expression of HMGB1, TNF-α, IL-1β and Iba-1 other than APP mRNA was down-regulated in SE group.

Conclusion

Ethyl pyruvate can relieve cognitive dysfunction that induced by sepsis, which may be associated with inflammation reduction and blood-brain barrier function improvement.

Key words: Ethyl pyruvate, Sepsis-associated encephalopathy, High-mobility protein group 1

Qun Chen, Weihua Lu, Yingya Cao, Xuemei Qin, Xiaogan Jiang, Guanggui Shen, Zhen Wang. Effect of ethyl pyruvate on cognitive function in sepsis rats[J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2018, 04(02): 182-189.

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Figures/Tables 9

References 20

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组别	第1天	第2天	第3天	第4天	第5天	第6天
C组（20只）	727.62±122.14	519.25±149.47	433.00±177.10	323.31±117.69	233.08±71.99	152.91±82.78
S组（11只）	769.58±248.25	676.96±304.60^a	564.99±232.47^a	546.71±308.04^a	431.59±308.31^a	319.00±206.98^a
SH组（8只）	720.17±255.52	487.61±255.93^ab	510.18±196.21^a	410.91±189.13^ab	474.11±285.38^a	362.03±210.40^ab
H组（18只）	752.52±186.92	682.84±227.27^a	546.76±290.58^a	407.88±210.46^ab	288.69±158.65^a	259.78±111.69^a
SE组（13只）	689.53±221.49	464.61±315.72^ab	471.38±260.15^ab	450.62±319.49^ab	340.81±191.78^ab	197.39±98.73^ab

组别	第1天	第2天	第3天	第4天	第5天	第6天
C组（20只）	727.62±122.14	519.25±149.47	433.00±177.10	323.31±117.69	233.08±71.99	152.91±82.78
S组（11只）	769.58±248.25	676.96±304.60^a	564.99±232.47^a	546.71±308.04^a	431.59±308.31^a	319.00±206.98^a
SH组（8只）	720.17±255.52	487.61±255.93^ab	510.18±196.21^a	410.91±189.13^ab	474.11±285.38^a	362.03±210.40^ab
H组（18只）	752.52±186.92	682.84±227.27^a	546.76±290.58^a	407.88±210.46^ab	288.69±158.65^a	259.78±111.69^a
SE组（13只）	689.53±221.49	464.61±315.72^ab	471.38±260.15^ab	450.62±319.49^ab	340.81±191.78^ab	197.39±98.73^ab

组别	第1天	第2天	第3天	第4天	第5天	第6天
C组（20只）	31.99±4.37	25.51±6.42	20.11±5.31	13.67±4.05	11.78±4.49	13.37±5.74
S组（11只）	31.83±9.90	29.69±7.44	22.61±6.71	26.46±9.81^a	19.48±7.57^a	19.89±11.45^a
SH组（8只）	35.31±11.70	30.07±14.90	32.65±13.09^ab	31.37±14.82^ab	31.64±15.61^ab	26.64±12.39^ab
H组（18只）	37.70±9.72	35.41±13.64	29.40±12.03^ab	24.54±9.35^a	17.67±8.33^a	16.41±8.57^a
SE组（13只）	29.49±9.81	25.61±16.13	23.86±18.96	25.33±13.75^a	19.32±10.24^a	14.24±11.87^ab

组别	第1天	第2天	第3天	第4天	第5天	第6天
C组（20只）	31.99±4.37	25.51±6.42	20.11±5.31	13.67±4.05	11.78±4.49	13.37±5.74
S组（11只）	31.83±9.90	29.69±7.44	22.61±6.71	26.46±9.81^a	19.48±7.57^a	19.89±11.45^a
SH组（8只）	35.31±11.70	30.07±14.90	32.65±13.09^ab	31.37±14.82^ab	31.64±15.61^ab	26.64±12.39^ab
H组（18只）	37.70±9.72	35.41±13.64	29.40±12.03^ab	24.54±9.35^a	17.67±8.33^a	16.41±8.57^a
SE组（13只）	29.49±9.81	25.61±16.13	23.86±18.96	25.33±13.75^a	19.32±10.24^a	14.24±11.87^ab

组别	第1天	第2天	第3天	第4天	第5天	第6天
C组（20只）	19.88±3.49	22.15±4.71	19.73±4.67	20.90±5.30	24.30±5.93	20.99±4.21
S组（11只）	23.23±3.20	23.44±3.73	21.70±5.78	22.73±4.60	23.88±4.45	22.48±4.21
SH组（8只）	20.35±2.88	16.44±3.14	16.65±5.46	14.77±4.59	15.29±5.43	14.32±4.79
H组（18只）	20.43±4.12	20.05±4.08	18.02±3.68	16.03±3.62	16.11±4.15	16.64±3.28
SE组（13只）	17.82±9.50	18.10±2.66	19.24±4.99	17.76±5.25	17.76±4.61	15.39±5.85

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