title: Monosialotetrahexosylganglioside protect cerebral ischemia/reperfusion injury through upregulating the expression of tyrosine hydroxylase by inhibiting lipid peroxidation.
abstract: To explore the new mechanism of neuroprtection of monosialotetrahexosylganglioside and providing reliable theoretical foundation and experimental evidence for the emergency treatment and rehabilitation of cerebral ischemia/reperfusion injury. A rat model of cerebral ischemia/reperfusion injury was constructed and intervened with monosialotetrahexosylganglioside(5mg/kg) and lipid peroxidation inhibitor U-101033E(40mg/kg). TTC straining and neurobiological function score were used to evaluate brain injury. 4-HNE and MDA content were measured to evaluate lipid peroxidation. The expression of tyrosine hydroxilase at both mRNA and protein levels and enzyme activity were determined to evaluate the gene disfunction. Tyrosine content in brain and in serum and the DOPA content in plasma were measured to evaluate the metabolism of tyrosine. As the study shown, cerebral ischemia/reperfusion lead to brain infarction and neurobiological function losing accompany with upregulation of 4-HNE and MDA levels and downregulation of TH expression (mRNA and protein) and decreased enzyme activity. The results above mentioned can be reversed obviously by intervening with monosialotetrahexosylganglioside and lipid peroxidation inhibitor U-101033E. Toxic aldehyde accumulation leaded to disfunction of tyrosine hydroxylase and excessive tyrosine and decreased synthesis of catecholamine neurotransmitter such as dopamine and accelerated neuron cell injury. Both monosialotetrahexosylganglioside and U-101033E presented neuroprotecion by restoring the tyrosine/dopa pathway through reversing the function of tyrosine hydroxylase by inhibiting lipid peroxidation.
authors.affiliation: Department of Medical Foundation of ChangSha Health Vocational College, Changsha 410100, China.
authors.lastname: Li-Mao
authors.affiliation: Department of Parmacy of Affiliated ChangSha Hospital of HuNan Normal University, Changsha 410006, China.
authors.forename: Yin-Juan
authors.initials: YJ
authors.lastname: Liao
authors.affiliation: Department of Parmacy of Affiliated ChangSha Hospital of HuNan Normal University, Changsha 410006, China.
authors.forename: Guang-Han
authors.initials: GH
authors.lastname: Hou
authors.affiliation: Department of Parmacy of Affiliated ChangSha Hospital of HuNan Normal University, Changsha 410006, China. Electronic address: 270769522@qq.com.
authors.forename: Zhong-Bao
authors.initials: ZB
authors.lastname: Yang
authors.affiliation: Department of Parmacy of Affiliated ChangSha Hospital of HuNan Normal University, Changsha 410006, China. Electronic address: 1762985079@qq.com.
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Zuo
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000517:prevention & control; D005227:Fatty Acids / Q000494:pharmacology / Q000627:therapeutic use*; D005677:G(M1) Ganglioside / Q000494:pharmacology / Q000627:therapeutic use*; D015971:Gene Expression Regulation, Enzymologic; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D011743:Pyrimidines / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D005227:Fatty Acids; D018696:Neuroprotective Agents; D011743:Pyrimidines; D011759:Pyrrolidines; C101923:U 101033E; C013584:lipid peroxidation inhibitor; D005677:G(M1) Ganglioside; D014446:Tyrosine 3-Monooxygenase
keywords: Cerebral ischemia/reperfusion injury; Lipid peroxidation; Monosialotetrahexosylganglioside(GM1); Tyrosine Hydroxylase(TH); Tyrosine/dopa pathway