title: Tetramethylpyrazine upregulates the aquaporin 8 expression of hepatocellular mitochondria in septic rats.
abstract: BACKGROUND
  The sepsis-induced acute liver injury majorly depends on the dysfunction of mitochondria and the loss of cellular energy. Aquaporin 8 (AQP8) can modulate water transport and osmotic swelling of mitochondria in the inner mitochondrial membrane of the liver. In this study, we explore the effects of tetramethylpyrazine (TMP) on protecting the structure of hepatocyte mitochondria and modulating the expression of AQP8.
  
  
  METHODS
  Forty-eight rats were randomly allocated to four groups: control group receiving sham procedure, septic group receiving cecal ligation and puncture (CLP), therapeutic group receiving 60 mg/kg of ligustrazine (TMP) intravenously from caudal vein immediately after CLP, and preventive group receiving 60 mg/kg/d of ligustrazine intravenously from caudal vein for 7 d before CLP. The mitochondrial ultrastructure of rat liver was observed. The protein expression of AQP8 was assayed by Western blot. Analysis of AQP8 messenger RNA (mRNA) expression level was performed by the reverse transcription-polymerase chain reaction. The mean fluorescence intensity (MFI) of rhodamine 123 (Rh 123) was measured by flow cytometry. The serum tumor necrosis factor alpha (TNF-α) level was determined by the enzyme-linked immunosorbent assay.
  
  
  RESULTS
  The mitochondrial ultrastructure was markedly damaged in the septic group, whereas it was lightly damaged in the therapeutic and preventive groups. Compared with the control group, the AQP8 protein expression and MFI were significantly reduced, and the steady-state AQP8 mRNA and serum TNF-α levels were increased in the septic, therapeutic, and preventive groups. Compared with the septic group, the AQP8 protein expression and MFI were increased, and the steady-state AQP8 mRNA and serum TNF-α levels were decreased significantly in the therapeutic and preventive groups. There was no significant difference in morphologic characteristics, AQP8 protein level, AQP8 mRNA level, MFI, and serum TNF-α level between the therapeutic and the preventive groups. Linear positive correlation was observed between the AQP8 protein level and the MFI of Rh 123. Linear negative correlation was observed between the AQP8 protein level or the MFI of Rh 123 and serum TNF-α level.
  
  
  CONCLUSIONS
  TMP has protective effect on hepatocellular mitochondria from damage in sepsis by ameliorating the expression of AQP8 protein in liver mitochondria. The protective effect of TMP on the liver mitochondria might not have a difference between using TMP before or after the occurrence of sepsis.
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan, China; ICU, Anhui Provincial Hospital affiliated Anhui Medical University, Hefei, China.
authors.forename: Jin-quan
authors.initials: JQ
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Xiao-gen
authors.initials: XG
authors.lastname: Tao
authors.forename: Li
authors.initials: L
authors.lastname: Wei
authors.forename: Bao
authors.initials: B
authors.lastname: Liu
authors.forename: Le-le
authors.initials: LL
authors.lastname: Huang
authors.forename: Yu-guo
authors.initials: YG
authors.lastname: Chen
mesh_terms: D000818:Animals; D020346:Aquaporins / Q000235:genetics* / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004195:Disease Models, Animal; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D008107:Liver Diseases / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D011719:Pyrazines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D020346:Aquaporins; D002121:Calcium Channel Blockers; D011719:Pyrazines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C108330:aquaporin 8; C017953:tetramethylpyrazine
keywords: Aquaporin 8; Liver; Mitochondria; Sepsis; Tetramethylpyrazine