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Guizhi Decoction () Inhibits Cholinergic Transdifferentiation by Regulating Imbalance of NGF and LIF in Salt-Sensitive Hypertensive Heart Failure Rats. | LitMetric

AI Article Synopsis

  • The study aimed to investigate how sympathetic nerve factors like NGF and LIF differ in salt-sensitive hypertensive heart failure rats and to assess the effects of Guizhi Decoction on nerve function.
  • The research involved three groups of rats on a high-salt diet, where one group received Guizhi Decoction and the others received saline for comparison, followed by various tests to evaluate cardiac and sympathetic functions.
  • Results showed that Guizhi Decoction improved sympathetic nerve health by increasing levels of NGF, enhancing nerve fiber expression, and reducing inflammation and collagen deposition in the heart compared to the untreated model group.

Article Abstract

Objective: To observe the imbalance of anatomical and functional innervation factors of sympathetic nerves, nerve growth factor (NGF) and leukemia inhibitory factor (LIF), in salt-sensitive hypertensive heart failure rats and to explore the effects of treatment with Guizhi Decoction () on sympathetic remodeling by inhibiting cholinergic transdifferentiation.

Methods: SS-13 and Dahl salt-sensitive (DS) rats were divided into 3 groups: SS-13 group (control group, n=9), DS group (model group, n=9) and GS group (Guizhi Decoction, n=9). After 10 weeks of a high-salt diet, the GS group rats were given Guizhi Decoction and other two groups were given saline at an equal volume as a vehicle. After 4 weeks' intragastric administration, rats were executed to detect the relevant indicators. Echocardiography and plasma n-terminal pro-B type natriuretic peptide (NT-proBNP) levels were used to assess cardiac function. Noradrenaline (NA) levels in the plasma and myocardium were detected to evaluate the sympathetic function. NGF and LIF expression were detected in the myocardium by Western blot or quantitative real-time PCR. Double immunofluorescence or Western blot was used to detect tyrosine hydroxylase (TH), choline acetyltransferase (CHAT) and growth associated protein 43 (GAP43) in order to reflect anatomical and functional changes of sympathetic nerves.

Results: DS group had anatomical and functional deterioration of sympathetic nerves in the decompensation period of heart failure compared with SS-13 group. Compared with the DS group, Guizhi Decoction significantly decreased the expression of LIF mRNA/protein (P<0.01), increased the expression of NGF (P<0.05 or P<0.01), enhanced the levels of TH+/GAP43+ and TH+/CHAT+ positive nerve fibers (P<0.01), and improved the protein expression of TH and GAP43 in left ventricle, but had no effect on CHAT (P>0.05). Guizhi Decoction inhibited inflammatory infiltration and collagen deposition of myocardial injury, increased the content of myocardial NA (P<0.05), reduced the plasma NA level (P<0.01), improved cardiac function (P<0.01), and improved weight and blood pressure to some extent (P<0.05), compared with DS group.

Conclusions: Guizhi Decoction could inhibit cholinergic transdifferentiation of sympathetic nerves, improve the anatomical and functional denervation of sympathetic nerves, and delay the progression of decompensated heart failure. The mechanism may be associated with the correction of the imbalance of NGF and LIF.

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Source
http://dx.doi.org/10.1007/s11655-019-2706-6DOI Listing

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