小陷胸汤加味方对2型糖尿病大鼠肝损伤的保护作用及其机制

doi:10.13481/j.1671-587X.20230308

Abstract

Abstract:

Objective To discuss the protective effect of Modified Xiao-Xian-Xiong Decoction （MXD） on liver injury in the rats with type 2 diabetes mellitus（T2DM）， and to clarify its possible mechanism. Methods Fifty rats were fed with high sugar and high fat combined with intraperitoneal injection of streptozotocin （STZ） to establish the T2DM rat models.A total of 40 rats successful modeling were randomly divided into model group（given no drugs），metformin group（given 200 mg·kg^－1 metformin）， low dose of MXD group （given 630 mg·kg^－1 MXD），and high dose of MXD group（given 1 260 mg·kg^－1 MXD）， and there were 10 rats in each group； another 10 rats were selected as control group（given standard feed）. The body masses of the rats in various groups were detected；the fasting blood glucose （FBG） levels of the rats in various groups were detected； the activities of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in serum of the rats in various groups were detected by fully automated biochemical analyzer；the pathomorphology of liver tissue of the rats in various groups were detected by HE staining； enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of interleukin 1β （IL-1β）， interleukin 6 （IL-6）， tumor necrosis factor α （TNF-α） in serum； the levels of superoxide dismutase （SOD）， reductive glutathione （GSH）， and malondialdehyde （MDA） in liver tissue of the rats in various groups were measured by spectrophotometer；the expression levels of nuclear factor E2 related factor 2 （Nrf2） and heme oxygenase （HO-1） proteins in liver tissue of the rats in various groups were detected by Western blotting method. Results The rats in control group had moderate feeding and water intake，and the above indexes of the rats had no sudden increasing and decreasing；the rats in model group had typical symptoms of diabetes；compared with model group，the diabetes symptoms of the rats in meftormin group，low dose of MXD group，and high dose of MXD group had been improved to various degrees.Compared with control group， the body masses of the rats in model group were significantly decreased at different time points（P<0.01）， while the FBG levels were increased （P<0.01）； compared wtih model group，the levels of FBG of the rats in meftormin group，low dose of MXD group，and high dose of MXD group were decreased in the 2nd，3rd and 4th weeks after administration，and the levels of FBG of the rats in low dose of MXD group were decreased in the 3rd and 4th weeks after administration（P<0.05 or P<0.01）.Compared with control group，the activities of AST and ALT in serum of the rats in model group were increased（P<0.01）；compared with model group，the activities of AST and ALT in serum of the rats in metformin group，low dose of MXD group，and high dose of MXD group were decreased（P<0.01）.The HE staining results showed that the morphology of liver cells of the rats in control group was normal，and there was no inflammatory cell infiltration；there was serious inflammatory cell infiltration in model group；there was a bit of inflammatory cell infiltration in meftormin group；there were almost no inflammatory cell infiltrations in low and high doses of MXD groups.The ELISA method results showed that the levels of serum IL-1β， IL-6， and TNF- α in serum of the rats in model group were significantly increased （P<0.01）.Compared with model group， the levels of serum IL-1β， IL-6， and TNF-α of the rats in metformin group， low dose of MXD and high dose of MXD groups were decreased（P<0.01）， while the activity of SOD， the level of GSH， and the expression levels of Nrf2 and HO-1 proteins in liver tissue of the rats in model group were significantly decreased （P<0.01）.The spectrophotometer results showed that compared with control group， the activity of SOD， the level of GSH in liver tissue of the rats in model group were decreased（P<0.01）， and the level of MDA was significantly increased （P<0.01）；compared with model group，the activities of SOD and the levels of GSH in liver tissue of the rats in metformin group，low dose of MXD group，and high dose of MXD group were decreased（P<0.01），and the levels of MDA in liver tissue of the rats in low and high doses of MXD groups were decreased（P<0.05 or P<0.01）.The Western blotting results showed that compared with control group，the expression levels of Nrf2 and HO-1 proteins in liver tissue of the rats in model group were decreased（P<0.01）；compared with model group， the expression levels of Nrf2 and HO-1 proteins in liver tissue of the rats in metformin group，low dose of MXD group，and high dose of MXD group were increased（P<0.05 or P<0.01）. Conclusion MXD has protective effect on liver injury of the rats with type 2 diabetes， and its mechanism may be related to anti-inflammation and activation of Nrf2/HO-1 signaling pathway，thereby inhibition of oxidative stress.

Key words: Modified Xiao-Xian-Xiong decoction, Type 2 diabetes mellitus, Liver injury, Inflammatory response, Oxidative stress

CLC Number:

R285.5

Jing GUAN,Shen HA,Hao YUAN,Ying CHEN,Pengju LIU,Zhi LIU,Shuang JIANG. Protective effect of Modified Xiao-Xian-Xiong Decoction on liver injury in rats with type 2 diabete mellitus and its mechanism[J].Journal of Jilin University(Medicine Edition), 2023, 49(3): 608-616.

Figures/Tables 7

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References 28

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Group	Body mass
Group	Before administration	1 weeks after administration	2 weeks after administration	3 weeks after administration		4 weeks after administration
Control	307.61±3.34	316.32±11.95	325.40±12.64	340.59±11.02	361.10±12.79
Model	303.45±22.41	265.19±30.98^*	242.24±27.48^*	234.23±24.75^*	219.89±23.82^*
Metformin	308.24±23.86	288.33±21.93	255.85±25.78	255.83±25.38	242.63±27.65
Low dose of MXD	310.42±37.47	281.80±40.95	261.11±30.92	255.01±41.42	230.78±24.81
High dose of MXD	309.96±17.18	278.04±14.79	251.36±11.24	249.07±13.67	232.56±17.48

Group	FBG level
Group	Before administration		1 weeks after administration		2 weeks after administration		3 weeks after administration		4 weeks after administration
Control	5.04±0.55	5.78±0.48		6.09±0.83		5.49±0.54		5.37±0.68
Model	18.89±1.92^*	19.24±1.56^*		18.81±1.64^*		18.72±4.04^*		17.99±2.55^*
Metformin	20.34±3.18	18.52±1.60		15.92±2.21^△△		13.55±1.79^△△		11.21±1.03^△△
Low dose of MXD	19.97±1.93	20.79±3.94		18.13±3.06		14.88±4.87^△		11.79±3.57^△△
High dose of MXD	20.34±3.20	18.66±3.07		16.04±2.81^△△		12.05±2.84^△△		11.08±2.74^△△

Group	ALT activity	AST activity
Control	83.87±19.21	110.54±16.27
Model	435.73±59.65^*	601.46±77.78^*
Metformin	166.09±31.83^△	298.42±34.49^△
Low dose of MXD	93.71±17.68^△	204.78±13.66^△
High dose of MXD	86.26±13.05^△	169.92±12.61^△

Group	IL-1β	IL-6	TNF-α
Control	23.58±6.75	31.13±4.42	72.90±12.03
Model	46.79±6.02^*	157.21±8.10^*	286.78±33.39^*
Metformin	28.49±4.26^△	84.60±5.51^△	188.02±16.60^△
Low dose of MXD	30.82±4.71^△	80.82±4.65^△	151.86±18.59^△
High dose of MXD	27.04±3.08^△	51.86±2.23^△	60.59±9.56^△

Group	SOD [λ_B/(U·mg^－1)]	GSH [m_B/(μmol·g^－1)]	MDA [m_B/(nmol·g^－1)]
Control	180.52±11.69	290.22±45.94	4.35±0.57
Model	96.85±13.76^*	38.21±5.80^*	9.77±2.16^*
Metformin	156.36±13.48^△△	55.79±7.05^△△	8.03±1.38
Low dose of MXD	129.70±16.82^△△	114.09±25.13^△△	7.35±1.31^△
High dose of MXD	145.58±15.67^△△	122.98±13.48^△△	5.09±0.86^△△

Protective effect of Modified Xiao-Xian-Xiong Decoction on liver injury in rats with type 2 diabete mellitus and its mechanism

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