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Electroacupuncture Ameliorates Acute Renal Injury in Lipopolysaccharide-Stimulated Rabbits via Induction of HO-1 through the PI3K/Akt/Nrf2 Pathways.

Yu JB, Shi J, Zhang Y, Gong LR, Dong SA, Cao XS, Wu LL, Wu LN - PLoS ONE (2015)

Bottom Line: The phosphatidylinositol 3-kinase (PI3K)-Akt pathway mediated the activation of NF-E2 related factor-2 (Nrf2), which was involved in HO-1 induction.Furthermore, partial protective effects of elecroacupuncture were counteracted by preconditioning with wortmannin (the selective PI3K inhibitor), indicating a direct involvement of PI3K/Akt pathway.Inconsistently, wortmannin pretreatment made little difference to the expressions of HO-1, Nrf2 nucleoprotein and total protein, which indicated that PI3K/Akt may be not the only pathway responsible for electroacupuncture-afforded protection against LPS-induced AKI.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin, China.

ABSTRACT
Electroacupuncture at select acupoints have been verified to protect against organ dysfunctions during endotoxic shock. And, heme oxygenase (HO)-1 as a phase II enzyme and antioxidant contributed to the protection of kidney in septic shock rats. The phosphatidylinositol 3-kinase (PI3K)-Akt pathway mediated the activation of NF-E2 related factor-2 (Nrf2), which was involved in HO-1 induction. To understand the efficacy of electroacupuncture stimulation in ameliorating acute kidney injury (AKI) through the PI3K/Akt/Nrf2 pathway and subsequent HO-1 upregulation, a dose of LPS 5mg/kg was administered intravenously to replicate the rabbit model of AKI induced by endotoxic shock. Electroacupuncture pretreatment was handled bilaterally at Zusanli and Neiguan acupoints for five consecutive days while sham electroacupuncture at non-acupoints as control. Results displayed that electroacupuncture stimulation significantly alleviated the morphologic renal damage, attenuated renal tubular apoptosis, suppressed the elevated biochemical indicators of AKI caused by LPS, enhanced the expressions of phospho-Akt, HO-1protein, Nrf2 total and nucleoprotein, and highlighted the proportions of Nrf2 nucleoprotein as a parallel. Furthermore, partial protective effects of elecroacupuncture were counteracted by preconditioning with wortmannin (the selective PI3K inhibitor), indicating a direct involvement of PI3K/Akt pathway. Inconsistently, wortmannin pretreatment made little difference to the expressions of HO-1, Nrf2 nucleoprotein and total protein, which indicated that PI3K/Akt may be not the only pathway responsible for electroacupuncture-afforded protection against LPS-induced AKI. These findings provide new insights into the potential future clinical applications of electroacupuncture for AKI induced by endotoxic shock instead of traditional remedies.

No MeSH data available.


Related in: MedlinePlus

Microphotographs of histopathologic changes of kidney sections stained with hematoxylin and eosin.(original magnification×400): (W, C) Normal morphology of kidneys; (L, SEL) Rabbits treated with LPS or sham electroacupuncture showing infiltration of inflammatory cells, tubular epithelial cell vacuolization, swelling and desquamation. (EL) Marked attenuation of tubular damages were displayed in treatment with electroacupuncture at ST36 and PC6 acupoints. (ELW) Preprocessing with wortmannin suppressed the protective efficacy of electroacupuncture to some extent. Black arrows: the destruction of renal capsule and capsular space in group ELW while infiltration of inflammatory cells in group EL or group SEL.
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pone.0141622.g003: Microphotographs of histopathologic changes of kidney sections stained with hematoxylin and eosin.(original magnification×400): (W, C) Normal morphology of kidneys; (L, SEL) Rabbits treated with LPS or sham electroacupuncture showing infiltration of inflammatory cells, tubular epithelial cell vacuolization, swelling and desquamation. (EL) Marked attenuation of tubular damages were displayed in treatment with electroacupuncture at ST36 and PC6 acupoints. (ELW) Preprocessing with wortmannin suppressed the protective efficacy of electroacupuncture to some extent. Black arrows: the destruction of renal capsule and capsular space in group ELW while infiltration of inflammatory cells in group EL or group SEL.

Mentions: As shown in Fig 3, no abnormal structures were visible in group C and group W. In comparison, kidney tissues from LPS group had extensive cellular vacuolization, swelling and desquamation in proximal tubules, interstitial edema and neutrophil infiltration. There was a distinct reduction in the extent of morphological damage in rabbits treated with electroacupuncture at ST36 and PC6. However, preprocessing with wortmannin suppressed the efficacy of electroacupuncture treatment. The results, presented as the scores of acute kidney injury, were summarized in Table 2. Consistently, the levels of kidney injury scores in group EL were lower than group L, and higher than group ELW (P<0.05). Meanwhile, similar results were observed in group SEL and group L (P>0.05).


Electroacupuncture Ameliorates Acute Renal Injury in Lipopolysaccharide-Stimulated Rabbits via Induction of HO-1 through the PI3K/Akt/Nrf2 Pathways.

Yu JB, Shi J, Zhang Y, Gong LR, Dong SA, Cao XS, Wu LL, Wu LN - PLoS ONE (2015)

Microphotographs of histopathologic changes of kidney sections stained with hematoxylin and eosin.(original magnification×400): (W, C) Normal morphology of kidneys; (L, SEL) Rabbits treated with LPS or sham electroacupuncture showing infiltration of inflammatory cells, tubular epithelial cell vacuolization, swelling and desquamation. (EL) Marked attenuation of tubular damages were displayed in treatment with electroacupuncture at ST36 and PC6 acupoints. (ELW) Preprocessing with wortmannin suppressed the protective efficacy of electroacupuncture to some extent. Black arrows: the destruction of renal capsule and capsular space in group ELW while infiltration of inflammatory cells in group EL or group SEL.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4629879&req=5

pone.0141622.g003: Microphotographs of histopathologic changes of kidney sections stained with hematoxylin and eosin.(original magnification×400): (W, C) Normal morphology of kidneys; (L, SEL) Rabbits treated with LPS or sham electroacupuncture showing infiltration of inflammatory cells, tubular epithelial cell vacuolization, swelling and desquamation. (EL) Marked attenuation of tubular damages were displayed in treatment with electroacupuncture at ST36 and PC6 acupoints. (ELW) Preprocessing with wortmannin suppressed the protective efficacy of electroacupuncture to some extent. Black arrows: the destruction of renal capsule and capsular space in group ELW while infiltration of inflammatory cells in group EL or group SEL.
Mentions: As shown in Fig 3, no abnormal structures were visible in group C and group W. In comparison, kidney tissues from LPS group had extensive cellular vacuolization, swelling and desquamation in proximal tubules, interstitial edema and neutrophil infiltration. There was a distinct reduction in the extent of morphological damage in rabbits treated with electroacupuncture at ST36 and PC6. However, preprocessing with wortmannin suppressed the efficacy of electroacupuncture treatment. The results, presented as the scores of acute kidney injury, were summarized in Table 2. Consistently, the levels of kidney injury scores in group EL were lower than group L, and higher than group ELW (P<0.05). Meanwhile, similar results were observed in group SEL and group L (P>0.05).

Bottom Line: The phosphatidylinositol 3-kinase (PI3K)-Akt pathway mediated the activation of NF-E2 related factor-2 (Nrf2), which was involved in HO-1 induction.Furthermore, partial protective effects of elecroacupuncture were counteracted by preconditioning with wortmannin (the selective PI3K inhibitor), indicating a direct involvement of PI3K/Akt pathway.Inconsistently, wortmannin pretreatment made little difference to the expressions of HO-1, Nrf2 nucleoprotein and total protein, which indicated that PI3K/Akt may be not the only pathway responsible for electroacupuncture-afforded protection against LPS-induced AKI.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin, China.

ABSTRACT
Electroacupuncture at select acupoints have been verified to protect against organ dysfunctions during endotoxic shock. And, heme oxygenase (HO)-1 as a phase II enzyme and antioxidant contributed to the protection of kidney in septic shock rats. The phosphatidylinositol 3-kinase (PI3K)-Akt pathway mediated the activation of NF-E2 related factor-2 (Nrf2), which was involved in HO-1 induction. To understand the efficacy of electroacupuncture stimulation in ameliorating acute kidney injury (AKI) through the PI3K/Akt/Nrf2 pathway and subsequent HO-1 upregulation, a dose of LPS 5mg/kg was administered intravenously to replicate the rabbit model of AKI induced by endotoxic shock. Electroacupuncture pretreatment was handled bilaterally at Zusanli and Neiguan acupoints for five consecutive days while sham electroacupuncture at non-acupoints as control. Results displayed that electroacupuncture stimulation significantly alleviated the morphologic renal damage, attenuated renal tubular apoptosis, suppressed the elevated biochemical indicators of AKI caused by LPS, enhanced the expressions of phospho-Akt, HO-1protein, Nrf2 total and nucleoprotein, and highlighted the proportions of Nrf2 nucleoprotein as a parallel. Furthermore, partial protective effects of elecroacupuncture were counteracted by preconditioning with wortmannin (the selective PI3K inhibitor), indicating a direct involvement of PI3K/Akt pathway. Inconsistently, wortmannin pretreatment made little difference to the expressions of HO-1, Nrf2 nucleoprotein and total protein, which indicated that PI3K/Akt may be not the only pathway responsible for electroacupuncture-afforded protection against LPS-induced AKI. These findings provide new insights into the potential future clinical applications of electroacupuncture for AKI induced by endotoxic shock instead of traditional remedies.

No MeSH data available.


Related in: MedlinePlus