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Berberine ameliorates the neurological dysfunction of the gastric fundus by promoting calcium channels dependent release of ACh in STZ-induced diabetic rats
Affiliation:1. College of Pharmacy, Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang 050017, PR China;2. Beijing Shouyi Group Co., Ltd. Mine Hospital, Tangshan 064400, PR China
Abstract:BackgroundIt has been reported diabetic gastroparesis is related to diabetic autonomic neuropathy of the gastrointestinal tract, and berberine (BBR) could ameliorate diabetic central and peripheral neuropathy. However, the influence of BBR on the function and motility of the gastric fundus nerve is unclear.MethodsA diabetic rat model was constructed, and HE staining was used to observe the morphological changes in the gastric fundus. The changes in cholinergic and nitrogen-related neurochemical indexes and the effects of BBR on them were measured using Elisa. The effects of BBR on the neural function and motility of gastric fundus were investigated by electric field stimulation (EFS) induced neurogenic response in vitro.ResultsIn the early stage of STZ-induced diabetic rats, the contractile response of gastric fundus induced by EFS was disorder, disturbance of contraction amplitude, and the cell bodies of neurons in the myenteric plexus of gastric fundus presented vacuolar lesions. Administration with BBR could improve the above symptoms. BBR further enhanced the contraction response in the presence of a NOS inhibitor or the case of inhibitory neurotransmitters removal. Interestingly, the activity of ACh could affect NO release directly and the enhancement of BBR on contractile response was canceled by calcium channel blockers completely.ConclusionsIn the early stage of STZ-induced diabetic rats, the neurogenic contractile response disorder of the gastric fundus is mainly related to cholinergic and nitrergic nerve dysfunction. BBR promotes the release of ACh mainly by affecting the calcium channel to improve the neurological dysfunction of the gastric fundus.
Keywords:Berberine  Contractile function  Gastric fundus  ACh  NO  Calcium channel  BBR"}  {"#name":"keyword"  "$":{"id":"k0040"}  "$$":[{"#name":"text"  "_":"Berberine  EFS"}  {"#name":"keyword"  "$":{"id":"k0050"}  "$$":[{"#name":"text"  "_":"Electrical field stimulation  NO"}  {"#name":"keyword"  "$":{"id":"k0070"}  "$$":[{"#name":"text"  "_":"Nitric oxide  NOS"}  {"#name":"keyword"  "$":{"id":"k0080"}  "$$":[{"#name":"text"  "_":"Nitric oxide Synthase  VIP"}  {"#name":"keyword"  "$":{"id":"k0090"}  "$$":[{"#name":"text"  "_":"Vasoactive intestinal peptide  ATP"}  {"#name":"keyword"  "$":{"id":"k0100"}  "$$":[{"#name":"text"  "_":"Adenosine triphosphate  STZ"}  {"#name":"keyword"  "$":{"id":"k0110"}  "$$":[{"#name":"text"  "_":"Streptozotocin  TTX"}  {"#name":"keyword"  "$":{"id":"k0120"}  "$$":[{"#name":"text"  "_":"Tetrodotoxin  AML"}  {"#name":"keyword"  "$":{"id":"k0130"}  "$$":[{"#name":"text"  "_":"Amlodipine besylate  ACh"}  {"#name":"keyword"  "$":{"id":"k0140"}  "$$":[{"#name":"text"  "_":"Acetylcholine  Atr"}  {"#name":"keyword"  "$":{"id":"k0150"}  "$$":[{"#name":"text"  "_":"Atropine sulfate  α-chy"}  {"#name":"keyword"  "$":{"id":"k0160"}  "$$":[{"#name":"text"  "_":"α-chymotrypsin  Sur"}  {"#name":"keyword"  "$":{"id":"k0170"}  "$$":[{"#name":"text"  "_":"Suramin hexasodium salt  CCh"}  {"#name":"keyword"  "$":{"id":"k0180"}  "$$":[{"#name":"text"  "_":"Carbachol hydrochloride  AChE"}  {"#name":"keyword"  "$":{"id":"k0200"}  "$$":[{"#name":"text"  "_":"Acetylcholine esterase
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